Tag: Pharmacotherapy

What is Amitriptyline?

Published on by Andrew Marshall2 Comments

Introduction

Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant (TCA) primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder (MDD) and a variety of pain syndromes from neuropathic pain to fibromyalgia to migraine and tension headaches. Due to the frequency and prominence of side effects, amitriptyline is generally considered a second-line therapy for these indications.

The most common side effects are dry mouth, drowsiness, dizziness, constipation, and weight gain. Of note is sexual dysfunction, observed primarily in males. Glaucoma, liver toxicity and abnormal heart rhythms are rare but serious side effects. Blood levels of amitriptyline vary significantly from one person to another, and amitriptyline interacts with many other medications potentially aggravating its side effects.

Amitriptyline was discovered in the late 1950s by scientists at Merck and approved by the US Food and Drug Administration (FDA) in 1961. It is on the World Health Organisation’s List of Essential Medicines. It is available as a generic medication. In 2019, it was the 94th most commonly prescribed medication in the United States, with more than 8 million prescriptions.

Brief History

Amitriptyline was first developed by the American pharmaceutical company Merck in the late 1950s. In 1958, Merck approached a number of clinical investigators proposing to conduct clinical trials of amitriptyline for schizophrenia. One of these researchers, Frank Ayd, instead, suggested using amitriptyline for depression. Ayd treated 130 patients and, in 1960, reported that amitriptyline had antidepressant properties similar to another, and the only known at the time, tricyclic antidepressant imipramine. Following this, the FDA approved amitriptyline for depression in 1961.

In Europe, due to a quirk of the patent law at the time allowing patents only on the chemical synthesis but not on the drug itself, Roche and Lundbeck were able to independently develop and market amitriptyline in the early 1960s.

According to research by the historian of psychopharmacology David Healy, amitriptyline became a much bigger selling drug than its precursor imipramine because of two factors. First, amitriptyline has much stronger anxiolytic effect. Second, Merck conducted a marketing campaign raising clinicians’ awareness of depression as a clinical entity.

Medical Uses

Amitriptyline is indicated for the treatment of major depressive disorder and neuropathic pain and for the prevention of migraine and chronic tension headache. It can be used for the treatment of nocturnal enuresis in children older than 6 after other treatments have failed.

Depression

Amitriptyline is effective for depression, but it is rarely used as a first-line antidepressant due to its higher toxicity in overdose and generally poorer tolerability. It can be tried for depression as a second-line therapy, after the failure of other treatments. For treatment-resistant adolescent depression or for cancer-related depression amitriptyline is no better than placebo. It is sometimes used for the treatment of depression in Parkinson’s disease, but supporting evidence for that is lacking.

Pain

Amitriptyline alleviates painful diabetic neuropathy. It is recommended by a variety of guidelines as a first or second line treatment. It is as effective for this indication as gabapentin or pregabalin but less well tolerated.

Low doses of amitriptyline moderately improve sleep disturbances and reduce pain and fatigue associated with fibromyalgia. It is recommended for fibromyalgia accompanied by depression by Association of the Scientific Medical Societies in Germany and as a second-line option for fibromyalgia, with exercise being the first line option, by European League Against Rheumatism. Combinations of amitriptyline and fluoxetine or melatonin may reduce fibromyalgia pain better than either medication alone.

There is some (low-quality) evidence that amitriptyline may reduce pain in cancer patients. It is recommended only as a second line therapy for non-chemotherapy-induced neuropathic or mixed neuropathic pain, if opioids did not provide the desired effect.

Moderate evidence exists in favour of amitriptyline use for atypical facial pain. Amitriptyline is ineffective for HIV-associated neuropathy.

Headache

Amitriptyline is probably effective for the prevention of periodic migraine in adults. Amitriptyline is similar in efficacy to venlafaxine and topiramate but carries a higher burden of adverse effects than topiramate. For many patients, even very small doses of amitriptyline are helpful, which may allow for minimization of side effects. Amitriptyline is not significantly different from placebo when used for the prevention of migraine in children.

Amitriptyline may reduce the frequency and duration of chronic tension headache, but it is associated with worse adverse effects than mirtazapine. Overall, amitriptyline is recommended for tension headache prophylaxis, along with lifestyle advice, which should include avoidance of analgesia and caffeine.

Other Indications

Amitriptyline is effective for the treatment of irritable bowel syndrome; however, because of its side effects, it should be reserved for select patients for whom other agents do not work. There is insufficient evidence to support its use for abdominal pain in children with functional gastrointestinal disorders.

Tricyclic antidepressants decrease the frequency, severity, and duration of cyclic vomiting syndrome episodes. Amitriptyline, as the most commonly used of them, is recommended as a first-line agent for its therapy.

Amitriptyline may improve pain and urgency intensity associated with bladder pain syndrome and can be used in the management of this syndrome. Amitriptyline can be used in the treatment of nocturnal enuresis in children. However, its effect is not sustained after the treatment ends. Alarm therapy gives better short- and long-term results.

In the US, amitriptyline is commonly used in children with ADHD as an adjunct to stimulant medications without any evidence or guideline supporting this practice. Many physicians in the UK (and the US also) commonly prescribe amitriptyline for insomnia; however, Cochrane reviewers were not able to find any randomised controlled studies that would support or refute this practice.

Contraindications and Precautions

The known contraindications of amitriptyline are:

  • History of myocardial infarction.
  • History of arrhythmias, particularly any degree of heart block.
  • Coronary artery disease.
  • Porphyria.
  • Severe liver disease (such as cirrhosis).
  • Being under six years of age.
  • Patients who are taking monoamine oxidase inhibitors (MAOIs) or have taken them within the last 14 days.

Amitriptyline should be used with caution in patients with epilepsy, impaired liver function, pheochromocytoma, urinary retention, prostate enlargement, hyperthyroidism, and pyloric stenosis.

In patients with the rare condition of shallow anterior chamber of eyeball and narrow anterior chamber angle, amitriptyline may provoke attacks of acute glaucoma due to dilation of the pupil. It may aggravate psychosis, if used for depression with schizophrenia, or precipitate the switch to mania in those with bipolar disorder.

CYP2D6 poor metabolisers should avoid amitriptyline due to increased side effects. If it is necessary to use it, half dose is recommended. Amitriptyline can be used during pregnancy and lactation, in the cases when SSRI do not work.

Side Effects

The most frequent side effects, occurring in 20% or more of users, are dry mouth, drowsiness, dizziness, constipation, and weight gain (on average 1.8 kg). Other common side effects (in 10% or more) are vision problems (amblyopia, blurred vision), tachycardia, increased appetite, tremor, fatigue/asthenia/feeling slowed down, and dyspepsia.

A literature review about abnormal movements and amitriptyline found that this drug is associated with various movement disorders, particularly dyskinesia, dystonia, and myoclonus. Stuttering and restless legs syndrome are some of the less common associations.

A less common side effect of amitriptyline is urination problems (8.7%).

Amitriptyline-associated sexual dysfunction (occurring at a frequency of 6.9%) seems to be mostly confined to males with depression and is expressed predominantly as erectile dysfunction and low libido disorder, with lesser frequency of ejaculatory and orgasmic problems. The rate of sexual dysfunction in males treated for indications other than depression and in females is not significantly different from placebo.

Liver tests abnormalities occur in 10-12% of patients on amitriptyline, but are usually mild, asymptomatic and transient, with consistently elevated alanine transaminase in 3% of all patients. The increases of the enzymes above the 3-fold threshold of liver toxicity are uncommon, and cases of clinically apparent liver toxicity are rare; nevertheless, amitriptyline is placed in the group of antidepressants with greater risks of hepatic toxicity.

Amitriptyline prolongs the QT interval. This prolongation is relatively small at therapeutic doses but becomes severe in overdose.

Overdose

Refer to Tricyclic Antidepressant Overdose.

The symptoms and the treatment of an overdose are largely the same as for the other TCAs, including the presentation of serotonin syndrome and adverse cardiac effects. The British National Formulary notes that amitriptyline can be particularly dangerous in overdose, thus it and other TCAs are no longer recommended as first-line therapy for depression. The treatment of overdose is mostly supportive as no specific antidote for amitriptyline overdose is available. Activated charcoal may reduce absorption if given within 1-2 hours of ingestion. If the affected person is unconscious or has an impaired gag reflex, a nasogastric tube may be used to deliver the activated charcoal into the stomach. ECG monitoring for cardiac conduction abnormalities is essential and if one is found close monitoring of cardiac function is advised. Body temperature should be regulated with measures such as heating blankets if necessary. Cardiac monitoring is advised for at least five days after the overdose. Benzodiazepines are recommended to control seizures. Dialysis is of no use due to the high degree of protein binding with amitriptyline.

Interactions

Since amitriptyline and its active metabolite nortriptyline are primarily metabolised by cytochromes CYP2D6 and CYP2C19, the inhibitors of these enzymes are expected to exhibit pharmacokinetic interactions with amitriptyline. According to the prescribing information, the interaction with CYP2D6 inhibitors may increase the plasma level of amitriptyline. However, the results in the other literature are inconsistent: the co-administration of amitriptyline with a potent CYP2D6 inhibitor paroxetine does increase the plasma levels of amitriptyline two-fold and of the main active metabolite nortriptyline 1.5-fold, but combination with less potent CYP2D6 inhibitors thioridazine or levomepromazine does not affect the levels of amitriptyline and increases nortriptyline by about 1.5-fold; a moderate CYP2D6 inhibitor fluoxetine does not seem to have a significant effect on the levels of amitriptyline or nortriptyline. A case of clinically significant interaction with potent CYP2D6 inhibitor terbinafine has been reported.

A potent inhibitor of CYP2C19 and other cytochromes fluvoxamine increases the level of amitriptyline two-fold while slightly decreasing the level of nortriptyline. Similar changes occur with a moderate inhibitor of CYP2C19 and other cytochromes cimetidine: amitriptyline level increases by about 70%, while nortriptyline decreases by 50%. CYP3A4 inhibitor ketoconazole elevates amitriptyline level by about a quarter. On the other hand, cytochrome P450 inducers such as carbamazepine and St. John’s Wort decrease the levels of both amitriptyline and nortriptyline.

Oral contraceptives may increase the blood level of amitriptyline by as high as 90%. Valproate moderately increases the levels of amitriptyline and nortriptyline through an unclear mechanism.

The prescribing information warns that the combination of amitriptyline with monoamine oxidase inhibitors may cause potentially lethal serotonin syndrome; however, this has been disputed. The prescribing information cautions that some patients may experience a large increase in amitriptyline concentration in the presence of topiramate. However, other literature states that there is little or no interaction: in a pharmacokinetic study topiramate only increased the level of amitriptyline by 20% and nortriptyline by 33%.

Amitriptiline counteracts the antihypertensive action of guanethidine. When given with amitriptyline, other anticholinergic agents may result in hyperpyrexia or paralytic ileus. Co-administration of amitriptyline and disulfiram is not recommended due to the potential for the development of toxic delirium. Amitriptyline causes an unusual type of interaction with the anticoagulant phenprocoumon during which great fluctuations of the prothrombin time have been observed.

Pharmacology

Pharmacodynamics

Amitriptyline inhibits serotonin transporter (SERT) and norepinephrine transporter (NET). It is metabolised to nortriptyline, a stronger norepinephrine reuptake inhibitor, further augmenting amitriptyline’s effects on norepinephrine reuptake.

Amitriptyline additionally acts as a potent inhibitor of the serotonin 5-HT2A, 5-HT2C, the α1A-adrenergic, the histamine H1 and the M1-M5 muscarinic acetylcholine receptors.

Amitriptyline is a non-selective blocker of multiple ion channels, in particular, voltage-gated sodium channels Nav1.3, Nav1.5, Nav1.6, Nav1.7, and Nav1.8, voltage-gated potassium channels Kv7.2/ Kv7.3, Kv7.1, Kv7.1/KCNE1, and hERG.

Mechanism of Action

Inhibition of serotonin and norepinephrine transporters by amitriptyline results in interference with neuronal reuptake of serotonin and norepinephrine. Since the reuptake process is important physiologically in terminating transmitting activity, this action may potentiate or prolong activity of serotonergic and adrenergic neurons and is believed to underlie the antidepressant activity of amitriptyline.

Inhibition of norepinephrine reuptake leading to increased concentration of norepinephrine in the posterior grey column of the spinal cord appears to be mostly responsible for the analgesic action of amitriptyline. Increased level of norepinephrine increases the basal activity of alpha-2 adrenergic receptors, which mediate an analgesic effect by increasing gamma-aminobutyric acid transmission among spinal interneurons. The blocking effect of amitriptyline on sodium channels may also contribute to its efficacy in pain conditions.

Pharmacokinetics

Amitriptyline is readily absorbed from the gastrointestinal tract (90-95%). Absorption is gradual with the peak concentration in blood plasma reached after about 4 hours. Extensive metabolism on the first pass through the liver leads to average bioavailability of about 50% (45%-53%). Amitriptyline is metabolized mostly by CYP2C19 into nortriptyline and by CYP2D6 leading to a variety of hydroxylated metabolites, with the principal one among them being (E)-10-hydroxynortriptyline, and to a lesser degree, by CYP3A4.

Nortriptyline, the main active metabolite of amitriptyline, is an antidepressant on its own right. Nortriptyline reaches 10% higher level in the blood plasma than the parent drug amitriptyline and 40% greater area under the curve, and its action is an important part of the overall action of amitriptyline.

Another active metabolite is (E)-10-hydroxynortriptyline, which is a norepinephrine uptake inhibitor four times weaker than nortriptyline. (E)-10-hydroxynortiptyline blood level is comparable to that of nortriptyline, but its cerebrospinal fluid level, which is a close proxy of the brain concentration of a drug, is twice higher than nortriptyline’s. Based on this, (E)-10-hydroxynortriptyline was suggested to significantly contribute to antidepressant effects of amitriptyline.

Blood levels of amitriptyline and nortriptyline and pharmacokinetics of amitriptyline in general, with clearance difference of up to 10-fold, vary widely between individuals. Variability of the area under the curve in steady state is also high, which makes a slow upward titration of the dose necessary.

In the blood, amitriptyline is 96% bound to plasma proteins; nortriptyline is 93-95% bound, and (E)-10-hydroxynortiptyline is about 60% bound. Amitriptyline has an elimination half life of 21 hours, nortriptyline – 23-31 hours, and (E)-10-hydroxynortiptyline – 8-10 hours. Within 48 hours, 12-80% of amitriptyline is eliminated in the urine, mostly as metabolites. 2% of the unchanged drug is excreted in the urine. Elimination in the faeces, apparently, have not been studied.

Therapeutic levels of amitriptyline range from 75 to 175 ng/mL (270-631 nM), or 80-250 ng/mL of both amitriptyline and its metabolite nortriptyline.

Pharmacogenetics

Since amitriptyline is primarily metabolised by CYP2D6 and CYP2C19, genetic variations within the genes coding for these enzymes can affect its metabolism, leading to changes in the concentrations of the drug in the body. Increased concentrations of amitriptyline may increase the risk for side effects, including anticholinergic and nervous system adverse effects, while decreased concentrations may reduce the drug’s efficacy.

Individuals can be categorised into different types of CYP2D6 or CYP2C19 metabolisers depending on which genetic variations they carry. These metaboliser types include poor, intermediate, extensive, and ultrarapid metabolisers. Most individuals (about 77-92%) are extensive metabolisers, and have “normal” metabolism of amitriptyline. Poor and intermediate metabolisers have reduced metabolism of the drug as compared to extensive metabolisers; patients with these metaboliser types may have an increased probability of experiencing side effects. Ultrarapid metabolisers use amitriptyline much faster than extensive metabolisers; patients with this metaboliser type may have a greater chance of experiencing pharmacological failure.

The Clinical Pharmacogenetics Implementation Consortium recommends avoiding amitriptyline in patients who are CYP2D6 ultrarapid or poor metabolizers, due to the risk for a lack of efficacy and side effects, respectively. The consortium also recommends considering an alternative drug not metabolised by CYP2C19 in patients who are CYP2C19 ultrarapid metabolisers. A reduction in starting dose is recommended for patients who are CYP2D6 intermediate metabolisers and CYP2C19 poor metabolisers. If use of amitriptyline is warranted, therapeutic drug monitoring is recommended to guide dose adjustments. The Dutch Pharmacogenetics Working Group also recommends selecting an alternative drug or monitoring plasma concentrations of amitriptyline in patients who are CYP2D6 poor or ultrarapid metabolisers, and selecting an alternative drug or reducing initial dose in patients who are CYP2D6 intermediate metabolisers.

Chemistry

Amitriptyline is a highly lipophilic molecule having an octanol-water partition coefficient (pH 7.4) of 3.0, while the log P of the free base was reported as 4.92. Solubility of the free base amitriptyline in water is 14 mg/L. Amitriptyline is prepared by reacting dibenzosuberone with 3-(dimethylamino)propylmagnesium chloride and then heating the resulting intermediate product with hydrochloric acid to eliminate water.

Society and Culture

English folk singer Nick Drake died from an overdose of Tryptizol in 1974.

Senteni Masango, wife of Swaziland King Mswati, died on 6 April 2018 after committing suicide by overdosing on amytriptyline capsules.

In the 2021 film The Many Saints of Newark, amitriptyline (referred to by the brand name Elavil) is part of the plot line of the movie.

Generic Names

Amitriptyline is the English and French generic name of the drug and its INN, BAN, and DCF, while amitriptyline hydrochloride is its USAN, USP, BANM, and JAN. Its generic name in Spanish and Italian and its DCIT are amitriptilina, in German is Amitriptylin, and in Latin is amitriptylinum. The embonate salt is known as amitriptyline embonate, which is its BANM, or as amitriptyline pamoate unofficially.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Amitriptyline >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

An Overview of the Treatment of Bipolar Disorder

Published on by Andrew MarshallLeave a comment

Introduction

The emphasis of the treatment of bipolar disorder is on effective management of the long-term course of the illness, which can involve treatment of emergent symptoms.

Treatment methods include pharmacological and psychological techniques.

Principles

The primary treatment for bipolar disorder consists of medications called mood stabilisers, which are used to prevent or control episodes of mania or depression. Medications from several classes have mood stabilising activity. Many individuals may require a combination of medication to achieve full remission of symptoms. As it is impossible to predict which medication will work best for a particular individual, it may take some trial and error to find the best medication or combination for a specific patient. Psychotherapy also has a role in the treatment of bipolar disorder. The goal of treatment is not to cure the disorder but rather to control the symptoms and the course of the disorder. Generally speaking, maintenance treatment of bipolar disorder continues long after symptom control has been achieved.

Following diagnostic evaluation, the treating clinician must determine the optimal treatment setting in order to ensure the patient’s safety. Assessment of suicide risk is key, as the rate of suicide completion among those with bipolar disorder may be as high as 10-15%. Hospitalisation should be considered in patients whose judgement is significantly impaired by their illness, and those who have not responded to outpatient treatment; this may need to be done on an involuntary basis. Treatment setting should regularly be re-evaluated to ensure that it is optimal for the patient’s needs.

Mood Stabilisers

Lithium Salts

Lithium salts have been used for centuries as a first-line treatment for bipolar disorder. In ancient times, doctors would send their mentally ill patients to drink from “alkali springs” as a treatment. Although they were not aware of it, they were actually prescribing lithium, which was present in high concentration within the waters. The therapeutic effect of lithium salts appears to be entirely due to the lithium ion, Li+.

Its exact mechanism of action is uncertain, although there are several possibilities such as inhibition of inositol monophosphatase, modulation of G proteins or regulation of gene expression for growth factors and neuronal plasticity. There is strong evidence for its effectiveness in acute treatment and prevention of recurrence of mania. It can also be effective in bipolar depression, although the evidence is not as strong. It is also effective in reducing the risk of suicide in patients with mood disorders.

Potential side effects from lithium include gastrointestinal upset, tremor, sedation, excessive thirst, frequent urination, cognitive problems, impaired motor coordination, hair loss, and acne. Excessive levels of lithium can be harmful to the kidneys, and increase the risk of side effects in general. As a result, kidney function and blood levels of lithium are monitored in patients being treated with lithium. Therapeutic plasma levels of lithium range from 0.5 to 1.5 mEq/L, with levels of 0.8 or higher being desirable in acute mania.

Lithium levels should be above 0.6 mEq/L to reduce both manic and depressive episodes in patients. A recent review concludes that the standard lithium serum level should be 0.60-0.80 mmol/L with optional reduction to 0.40-0.60 mmol/L in case of good response but poor tolerance or an increase to 0.80-1.00 mmol/L in case of insufficient response and good tolerance.

Monitoring is generally more frequent when lithium is being initiated, and the frequency can be decreased once a patient is stabilised on a given dose. Thyroid hormones should also be monitored periodically, as lithium can increase the risk of hypothyroidism.

Anticonvulsants

A number of anti-convulsant drugs are used as mood stabilisers, and the suspected mechanism is related to the theory that mania can “kindle” further mania, similar to the kindling model of seizures. Valproic acid, or valproate, was one of the first anti-convulsants tested for use in bipolar disorder. It has proven to be effective for treating acute mania. The mania prevention and antidepressant effects of valproic acid have not been well demonstrated. Valproic acid is less effective than lithium at preventing and treating depressive episodes.

Carbamazepine was the first anti-convulsant shown to be effective for treating bipolar mania. It has not been extensively studied in bipolar depression. It is generally considered a second-line agent due to its side effect profile. Lamotrigine is considered a first-line agent for the treatment of bipolar depression. It is effective in preventing the recurrence of both mania and depression, but it has not proved useful in treating acute mania.

Zonisamide (trade name Zonegran), another anti-convulsant, also may show promise in treating bipolar depression. Various other anti-convulsants have been tested in bipolar disorder, but there is little evidence of their effectiveness. Other anti-convulsants effective in some cases and being studied closer include phenytoin, levetiracetam, pregabalin and valnoctamide.

Each anti-convulsant agent has a unique side-effect profile. Valproic acid can frequently cause sedation or gastrointestinal upset, which can be minimised by giving the related drug divalproex, which is available in an enteric-coated tablet. These side effects tend to disappear over time. According to studies conducted in Finland in patients with epilepsy, valproate may increase testosterone levels in teenage girls and produce polycystic ovary syndrome in women who began taking the medication before age 20. Increased testosterone can lead to polycystic ovary syndrome with irregular or absent menses, obesity, and abnormal growth of hair. Therefore, young female patients taking valproate should be monitored carefully by a physician. Excessive levels of valproate can lead to impaired liver function, and liver enzymes and serum valproate level, with a target of 50–125 µg/L, should be monitored periodically.

Side effects of carbamazepine include blurred vision, double vision, ataxia, weight gain, nausea, and fatigue, as well as some rare but serious side effects such as blood dyscrasias, pancreatitis, exfoliative dermatitis, and hepatic failure. Monitoring of liver enzymes, platelets, and blood cell counts are recommended.

Lamotrigine generally has minimal side effects, but the dose must be increased slowly to avoid rashes, including exfoliative dermatitis.

Atypical Antipsychotic Drugs

Antipsychotics work best in the manic phase of bipolar disorder. Second-generation or atypical antipsychotics (including aripiprazole, olanzapine, quetiapine, paliperidone, risperidone, and ziprasidone) have emerged as effective mood stabilisers. The evidence for this is fairly recent, as in 2003 the American Psychiatric Press noted that atypical anti-psychotics should be used as adjuncts to other anti-manic drugs because their mood stabilising properties had not been well established. The mechanism is not well known, but may be related to effects on glutamate activity. Several studies have shown atypical antipsychotics to be effective both as single-agent and adjunctive treatments. Antidepressant effectiveness varies, which may be related to different serotonergic and dopaminergic receptor binding profiles. Quetiapine and the combination of olanzapine and fluoxetine have both demonstrated effectiveness in bipolar depression.

In light of recent evidence, olanzapine (Zyprexa) has been US Food and Drug Administration (FDA) approved as an effective monotherapy for the maintenance of bipolar disorder. A head-to-head randomised control trial (RCT) in 2005 has also shown olanzapine monotherapy to be just as effective and safe as lithium in prophylaxis.

The atypical antipsychotics differ somewhat in side effect profiles, but most have some risk of sedation, weight gain, and extrapyramidal symptoms (including tremor, stiffness, and restlessness). They may also increase the risk of metabolic syndrome, so metabolic monitoring should be performed regularly, including checks of serum cholesterol, triglycerides, and glucose, weight, blood pressure, and waist circumference. Taking antipsychotics for long periods or at high doses can also cause tardive dyskinesia – a sometimes incurable neurological disorder resulting in involuntary, repetitive body movements. The risk of tardive dyskinesia appears to be lower in second-generation antipsychotics than in first-generation antipsychotics but as with first-generation drugs, increases with time spent on medications and in older patients.

New Treatments

A variety of other agents have been tried in bipolar disorder, including benzodiazepines, calcium channel blockers, L-methylfolate, and thyroid hormone. Modafinil (Provigil) and Pramipexole (Mirapex) have been suggested for treating cognitive dysfunction associated with bipolar depression, but evidence supporting their use is quite limited. In addition riluzole, a glutamatergic drug used in ALS has been studied as an adjunct or monotherapy treatment in bipolar depression, with mixed and inconsistent results. The selective oestrogen receptor modulator medication tamoxifen has shown rapid and robust efficacy treating acute mania in bipolar patients. This action is likely due not to tamoxifen’s oestrogen-modulating properties, but due to its secondary action as an inhibitor of protein Kinase C.

Cognitive Effects of Mood Stabilisers

Bipolar patients taking antipsychotics have lower scores on tests of memory and full-scale IQ than patients taking other mood stabilisers. Use of both typical and atypical antipsychotics is associated with risk of cognitive impairment, but the risk is higher for antipsychotics with more sedating effects.

Among bipolar patients taking anticonvulsants, those on lamotrigine have a better cognitive profile than those on carbamazepine, valproate, topiramate, and zonisamide.

Although decreased verbal memory and slowed psychomotor speed are common side effects of lithium use these side effects usually disappear after discontinuation of lithium. Lithium may be protective of cognitive function in the long term since it promotes neurogenesis in the hippocampus and increases grey matter volume in the prefrontal cortex.

Antidepressants

Antidepressants should only be used with caution in bipolar disorder, as they may not be effective and may even induce mania. They should not be used alone, but may be considered as an adjunct to lithium.

A recent large-scale study found that severe depression in patients with bipolar disorder responds no better to a combination of antidepressant medications and mood stabilisers than it does to mood stabilisers alone and that antidepressant use does not hasten the emergence of manic symptoms in patients with bipolar disorder.

The concurrent use of an antidepressant and a mood stabiliser, instead of mood stabiliser monotherapy, may lower the risk of further bipolar depressive episodes in patients whose most recent depressive episode has been resolved. However, some studies have also found that antidepressants pose a risk of inducing hypomania or mania, sometimes in individuals with no prior history of mania. Saint John’s Wort, although a naturally occurring compound, is thought to function in a fashion similar to man-made antidepressants, and so unsurprisingly, there are reports that suggest that it can also induce mania. For these reasons, some psychiatrists are hesitant to prescribe antidepressants for the treatment of bipolar disorder unless mood stabilisers have failed to have an effect, however, others feel that antidepressants still have an important role to play in treatment of bipolar disorder.

Side effects vary greatly among different classes of antidepressants.

Antidepressants are helpful in preventing suicides in people suffering from bipolar disorder when they go in for the depressive phase.

NMDA-Receptor Antagonists

In a double-blind, placebo-controlled, proof-of-concept study, researchers administered an N-methyl-d-aspartate-receptor antagonist (ketamine) to 18 patients already on treatment with lithium (10 patients) or valproate (8 patients) for bipolar depression. From 40 minutes following intravenous injection of ketamine hydrochloride (0.5 mg/kg), the researchers observed significant improvements in depressive symptoms, as measured by standard tools, that were maintained for up to 3 days, an effect not observed in subjects who received the placebo. Five subjects dropped out of the ketamine study; of these, four were taking valproate and one was being treated with lithium. One patient showed signs of hypomania following ketamine administration and two experienced low mood. This study demonstrates a rapid-onset antidepressant effect of ketamine in a small group of patients with bipolar depression. The authors acknowledged the study’s limitations, including the dissociative disturbances in patients receiving ketamine that could have compromised the study blinding, and they emphasised the need for further research.

A more recent double-blind, placebo-controlled study by the same group found that ketamine treatment resulted in a similarly rapid alleviation of suicidal ideation in 15 patients with bipolar depression.

Ketamine is used as a dissociative anaesthetic, and is a Class C substance in the United Kingdom; as such, it should only be used under the direction of a health professional.

Dopamine Agonists

In a single controlled study of twenty one patients, the dopamine D3 receptor agonist pramipexole was found to be highly effective in the treatment of bipolar depression. Treatment was initiated at 0.125 mg t.i.d. and increased at a rate of 0.125 mg t.i.d. to a limit of 4.5 mg qd until the patients’ condition satisfactorily responded to the medication or they could not abide the side effects. The final average dosage was 1.7 mg ± .90 mg qd. The incidence of hypomania in the treatment group was no greater than in the control group.

Psychotherapy

Certain types of psychotherapy, used in combination with medication, may provide some benefit in the treatment of bipolar disorders. Psychoeducation has been shown to be effective in improving patients’ compliance with their lithium treatment. Evidence of the efficacy of family therapy is not adequate to support unrestricted recommendation of its use. There is “fair support” for the utility of cognitive therapy. Evidence for the efficacy of other psychotherapies is absent or weak, often not being performed under randomised and controlled conditions. Well-designed studies have found interpersonal and social rhythm therapy to be effective.

Although medication and psychotherapy cannot cure the illness, therapy can often be valuable in helping to address the effects of disruptive manic or depressive episodes that have hurt a patient’s career, relationships or self-esteem. Therapy is available not only from psychiatrists but from social workers, psychologists and other licensed counsellors.

Jungian Therapy

Jungian authors have likened the mania and depression of bipolar disorder to the Jungian archetypes ‘puer’ and ‘senex’. The puer archetype is defined by the behaviours of spontaneity, impulsiveness, enthusiasm or mania and is symbolised by characters such as Peter Pan or the Greek god Hermes. The senex archetype is defined by behaviours of order, systematic thought, caution, and depression and is symbolised by characters such as the Roman god Saturn or the Greek god Kronos. Jungians conceptualise the puer and senex as a coexistent bipolarity appearing in human behaviour and imagination, but in neurotic manifestations appears as extreme oscillations and as unipolar manifestations. In the case of the split puer-senex bipolarity the therapeutic task is to bring the puer and senex back into correlation by working with the patient’s mental imagery.”

Lifestyle Changes

Sufficient Sleep

If sleeping is disturbed, the symptoms can occur. Sleep disruption may actually exacerbate the mental illness state. Those who do not get enough sleep at night, sleep late and wake up late, or go to sleep with some disturbance (e.g. music or charging devices) have a greater chance of having the symptoms and, in addition, depression. It is highly advised to not sleep too late and to get enough high quality sleep.

Self-Management and Self-Awareness

Understanding the symptoms, when they occur and ways to control them using appropriate medications and psychotherapy has given many people diagnosed with bipolar disorder a chance at a better life. Prodrome symptom detection has been shown to be used effectively to anticipate onset of manic episodes and requires high degree of understanding of one’s illness. Because the offset of the symptoms is often gradual, recognising even subtle mood changes and activity levels is important in avoiding a relapse. Maintaining a mood chart is a specific method used by patients and doctors to identify mood, environmental and activity triggers.

Stress Reduction

Forms of stress may include having too much to do, too much complexity and conflicting demands among others. There are also stresses that come from the absence of elements such as human contact, a sense of achievement, constructive creative outlets, and occasions or circumstances that will naturally elicit positive emotions. Stress reduction will involve reducing things that cause anxiety and increasing those that generate happiness. It is not enough to just reduce the anxiety.

Co-Morbid Substance Use Disorder

Co-occurring substance misuse disorders, which are extremely common in bipolar patients can cause a significant worsening of bipolar symptomatology and can cause the emergence of affective symptoms. The treatment options and recommendations for substance use disorders is wide but may include certain pharmacological and nonpharmacological treatment options.

Other Treatments

Omega-3 Fatty Acids

Omega-3 fatty acids may also be used as a treatment for bipolar disorder, particularly as a supplement to medication. An initial clinical trial by Stoll et al. (1999) produced positive results. However, since 1999 attempts to confirm this finding of beneficial effects of omega-3 fatty acids in several larger double-blind clinical trials have produced inconclusive results. It was hypothesized that the therapeutic ingredient in omega-3 fatty acid preparations is eicosapentaenoic acid (EPA) and that supplements should be high in this compound to be beneficial. A 2008 Cochrane systematic review found limited evidence to support the use of Omega-3 fatty acids to improve depression but not mania as an adjunct treatment for bipolar disorder.

Omega-3 fatty acids may be found in fish, fish oils, algae, and to a lesser degree in other foods such as flaxseed, flaxseed oil and walnuts. Although the benefits of Omega-3 fatty acids remain debated, they are readily available at drugstores and supermarkets, relatively inexpensive, and have few known side effects (All of these oils, however, have the capacity to exacerbate GERD (gastroesophageal reflux disease) – food sources may be a good alternative in such cases).

Exercise

Exercise has also been shown to have antidepressant effects.

Electroconvulsive Therapy

Electroconvulsive therapy (ECT) may have some effectiveness in mixed mania states, and good effectiveness in bipolar depression, particularly in the presence of psychosis. It may also be useful in the treatment of severe mania that is non-responsive to medications.

The most frequent side effects of ECT include memory impairment, headaches, and muscle aches. In some instances, ECT can produce significant and long-lasting cognitive impairment, including anterograde amnesia, and retrograde amnesia.

Ketogenic Diet

Because many of the medications that are effective in treating epilepsy are also effective as mood stabilizers, it has been suggested that the ketogenic diet – used for treating paediatric epilepsy – could have mood stabilising effects. Ketogenic diets are diets that are high in fat and low in carbohydrates, and force the body to use fat for energy instead of sugars from carbohydrates. This causes a metabolic response similar to that seen in the body during fasting. This idea has not been tested by clinical research, and until recently, was entirely hypothetical. Recently, however, two case studies have been described where ketogenic diets were used to treat bipolar II. In each case, the patients found that the ketogenic diet was more effective for treating their disorder than medication and were able to discontinue the use of medication. The key to efficacy appears to be ketosis (a metabolic state characterised by elevated levels of ketone bodies in the blood or urine), which can be achieved either with a classic high-fat ketogenic diet, or with a low-carbohydrate diet similar to the induction phase of the Atkins Diet. The mechanism of action is not well understood. It is unclear whether the benefits of the diet produce a lasting improvement in symptoms (as is sometimes the case in treatment for epilepsy) or whether the diet would need to be continued indefinitely to maintain symptom remission.

The Role of Cannabinoids

Acute cannabis intoxication transiently produces perceptual distortions, psychotic symptoms and reduction in cognitive abilities in healthy persons and in severe mental disorder, and may impair the ability to safely operate a motor vehicle.

Cannabis use is common in bipolar disorder, and is a risk factor for a more severe course of the disease by increasing frequency and duration of episodes. It is also reported to reduce age at onset.

Alternative Medicine

Several studies have suggested that omega-3 fatty acids may have beneficial effects on depressive symptoms, but not manic symptoms. However, only a few small studies of variable quality have been published and there is not enough evidence to draw any firm conclusions.

What is Conduct Disorder?

Published on by Andrew Marshall3 Comments

Introduction

Conduct disorder (CD) is a mental disorder diagnosed in childhood or adolescence that presents itself through a repetitive and persistent pattern of behaviour that includes theft, lies, physical violence that may lead to destruction and wanton breaking of rules, in which the basic rights of others or major age-appropriate norms are violated.

These behaviours are often referred to as “antisocial behaviours.” It is often seen as the precursor to antisocial personality disorder, which is per definition not diagnosed until the individual is 18 years old. Conduct disorder may result from parental rejection and neglect and can be treated with family therapy, as well as behavioural modifications and pharmacotherapy. Conduct disorder is estimated to affect 51.1 million people globally as of 2013.

Signs and Symptoms

One of the symptoms of conduct disorder is a lower level of fear. Research performed on the impact of toddlers exposed to fear and distress shows that negative emotionality (fear) predicts toddlers’ empathy-related response to distress. The findings support that if a caregiver is able to respond to infant cues, the toddler has a better ability to respond to fear and distress. If a child does not learn how to handle fear or distress the child will be more likely to lash out at other children. If the caregiver is able to provide therapeutic intervention teaching children at risk better empathy skills, the child will have a lower incident level of conduct disorder.

Increased instances of violent and antisocial behaviour are also associated with the condition; examples may range from pushing, hitting and biting when the child is young, progressing towards beating and inflicted cruelty as the child becomes older.

Conduct disorder can present with limited prosocial emotions, lack of remorse or guilt, lack of empathy, lack of concern for performance, and shallow or deficient affect. Symptoms vary by individual, but the four main groups of symptoms are described below.

Aggression to People and Animals

  • Often bullies, threatens or intimidates others.
  • Often initiates physical fights.
  • Has used a weapon that can cause serious physical harm to others (e.g., a bat, brick, broken bottle, knife, gun).
  • Has been physically cruel to people.
  • Has been physically cruel to animals.
  • Has stolen while confronting a victim (e.g. mugging, purse snatching, extortion, armed robbery).
  • Has forced someone into sexual activity (rape or molestation).
  • Feels no remorse or empathy towards the harm, fear, or pain they may have inflicted on others.

Destruction of Property

  • Has deliberately engaged in fire setting with the intention of causing serious damage.
  • Has deliberately destroyed others’ property (other than by fire setting).

Deceitfulness or Theft

  • Has broken into someone else’s house, building, or car.
  • Often lies to obtain goods or favours or to avoid obligations (i.e. “cons” others).
  • Has stolen items of nontrivial value without confronting a victim (e.g. shoplifting, but without breaking and entering; forgery).

Serious Violations of Rules

  • Often stays out at night despite parental prohibitions, beginning before age 13 years.
  • Has run away from home overnight at least twice while living in parental or parental surrogate home (or once without returning for a lengthy period).
  • Is often truant from school, beginning before age 13 years.

The lack of empathy these individuals have and the aggression that accompanies this carelessness for the consequences is dangerous – not only for the individual but for those around them.

Developmental Course

Currently, two possible developmental courses are thought to lead to conduct disorder. The first is known as the “childhood-onset type” and occurs when conduct disorder symptoms are present before the age of 10 years. This course is often linked to a more persistent life course and more pervasive behaviours. Specifically, children in this group have greater levels of ADHD symptoms, neuropsychological deficits, more academic problems, increased family dysfunction and higher likelihood of aggression and violence.

There is debate among professionals regarding the validity and appropriateness of diagnosing young children with conduct disorder. The characteristics of the diagnosis are commonly seen in young children who are referred to mental health professionals. A premature diagnosis made in young children, and thus labelling and stigmatising an individual, may be inappropriate. It is also argued that some children may not in fact have conduct disorder, but are engaging in developmentally appropriate disruptive behaviour.

The second developmental course is known as the “adolescent-onset type” and occurs when conduct disorder symptoms are present after the age of 10 years. Individuals with adolescent-onset conduct disorder exhibit less impairment than those with the childhood-onset type and are not characterised by similar psychopathology. At times, these individuals will remit in their deviant patterns before adulthood. Research has shown that there is a greater number of children with adolescent-onset conduct disorder than those with childhood-onset, suggesting that adolescent-onset conduct disorder is an exaggeration of developmental behaviours that are typically seen in adolescence, such as rebellion against authority figures and rejection of conventional values. However, this argument is not established and empirical research suggests that these subgroups are not as valid as once thought.

In addition to these two courses that are recognised by the DSM, there appears to be a relationship among oppositional defiant disorder, conduct disorder, and antisocial personality disorder. Specifically, research has demonstrated continuity in the disorders such that conduct disorder is often diagnosed in children who have been previously diagnosed with oppositional defiant disorder, and most adults with antisocial personality disorder were previously diagnosed with conduct disorder. For example, some research has shown that 90% of children diagnosed with conduct disorder had a previous diagnosis of oppositional defiant disorder. Moreover, both disorders share relevant risk factors and disruptive behaviours, suggesting that oppositional defiant disorder (ODD) is a developmental precursor and milder variant of conduct disorder. However, this is not to say that this trajectory occurs in all individuals. In fact, only about 25% of children with oppositional defiant disorder will receive a later diagnosis of conduct disorder. Correspondingly, there is an established link between conduct disorder and the diagnosis of antisocial personality disorder as an adult. In fact, the current diagnostic criteria for antisocial personality disorder require a conduct disorder diagnosis before the age of 15. However, again, only 25-40% of youths with conduct disorder will develop an antisocial personality disorder. Nonetheless, many of the individuals who do not meet full criteria for antisocial personality disorder still exhibit a pattern of social and personal impairments or antisocial behaviours. These developmental trajectories suggest the existence of antisocial pathways in certain individuals, which have important implications for both research and treatment.

Associated Conditions

Children with conduct disorder have a high risk of developing other adjustment problems. Specifically, risk factors associated with conduct disorder and the effects of conduct disorder symptomatology on a child’s psychosocial context have been linked to overlapping with other psychological disorders. In this way, there seems to be reciprocal effects of comorbidity with certain disorders, leading to increased overall risk for these youth.

Attention Deficit Hyperactivity Disorder

ADHD is the condition most commonly associated with conduct disorders, with approximately 25-30% of boys and 50-55% of girls with conduct disorder having a comorbid ADHD diagnosis. While it is unlikely that ADHD alone is a risk factor for developing conduct disorder, children who exhibit hyperactivity and impulsivity along with aggression is associated with the early onset of conduct problems. Moreover, children with comorbid conduct disorder and ADHD show more severe aggression.

Substance Use Disorders

Conduct disorder is also highly associated with both substance use and abuse. Children with conduct disorder have an earlier onset of substance use, as compared to their peers, and also tend to use multiple substances. However, substance use disorders themselves can directly or indirectly cause conduct disorder like traits in about half of adolescents who have a substance use disorder. As mentioned above, it seems that there is a transactional relationship between substance use and conduct problems, such that aggressive behaviours increase substance use, which leads to increased aggressive behaviour.

Substance use in conduct disorder can lead to antisocial behaviour in adulthood.

Schizophrenia

Conduct disorder is a precursor to schizophrenia in a minority of cases, with about 40% of men and 31% of women with schizophrenia meeting criteria for childhood conduct disorder.

Cause

While the cause of conduct disorder is complicated by an intricate interplay of biological and environmental factors, identifying underlying mechanisms is crucial for obtaining accurate assessment and implementing effective treatment. These mechanisms serve as the fundamental building blocks on which evidence-based treatments are developed. Despite the complexities, several domains have been implicated in the development of conduct disorder including cognitive variables, neurological factors, intraindividual factors, familial and peer influences, and wider contextual factors. These factors may also vary based on the age of onset, with different variables related to early (e.g. neurodevelopmental basis) and adolescent (e.g. social/peer relationships) onset.

Risks

The development of conduct disorder is not immutable or predetermined. A number of interactive risk and protective factors exist that can influence and change outcomes, and in most cases conduct disorder develops due to an interaction and gradual accumulation of risk factors. In addition to the risk factors identified under cause, several other variables place youth at increased risk for developing the disorder, including child physical abuse, in-utero alcohol exposure, and maternal smoking during pregnancy. Protective factors have also been identified, and most notably include high IQ, being female, positive social orientations, good coping skills, and supportive family and community relationships.

However, a correlation between a particular risk factor and a later developmental outcome (such as conduct disorder) cannot be taken as definitive evidence for a causal link. Co-variation between two variables can arise, for instance, if they represent age-specific expressions of similar underlying genetic factors. For example, the tendency to smoke during pregnancy (SDP) is subject to substantial genetic influence, as is conduct disorder. Thus, the genes that dispose the mother to SDP may also dispose the child to CD following mitotic transmission. Indeed, Rice et al. (2009) found that in mother-fetus pairs that were not genetically related (by virtue of in-vitro fertilisation), no link between SDP and later conduct problems arose. Thus, the distinction between causality and correlation is an important consideration.

Learning Disabilities

While language impairments are most common, approximately 20-25% of youth with conduct disorder have some type of learning disability. Although the relationship between the disorders is complex, it seems as if learning disabilities result from a combination of ADHD, a history of academic difficulty and failure, and long-standing socialisation difficulties with family and peers. However, confounding variables, such as language deficits, SES disadvantage, or neurodevelopmental delay also need to be considered in this relationship, as they could help explain some of the association between conduct disorder and learning problems.

Cognitive Factors

In terms of cognitive function, intelligence and cognitive deficits are common amongst youths with conduct disorder, particularly those with early-onset and have intelligence quotients (IQ) one standard deviation below the mean and severe deficits in verbal reasoning and executive function. Executive function difficulties may manifest in terms of one’s ability to shift between tasks, plan as well as organise, and also inhibit a prepotent response. These findings hold true even after taking into account other variables such as socioeconomic status (SES), and education. However, IQ and executive function deficits are only one piece of the puzzle, and the magnitude of their influence is increased during transactional processes with environmental factors.

Brain Differences

Beyond difficulties in executive function, neurological research on youth with conduct disorder also demonstrate differences in brain anatomy and function that reflect the behaviours and mental anomalies associated in conduct disorder. Compared to normal controls, youths with early and adolescent onset of conduct disorder displayed reduced responses in brain regions associated with social behaviour (i.e. amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex). In addition, youths with conduct disorder also demonstrated less responsiveness in the orbitofrontal regions of the brain during a stimulus-reinforcement and reward task. This provides a neural explanation for why youths with conduct disorder may be more likely to repeat poor decision making patterns. Lastly, youths with conduct disorder display a reduction in grey matter volume in the amygdala, which may account for the fear conditioning deficits. This reduction has been linked to difficulty processing social emotional stimuli, regardless of the age of onset. Aside from the differences in neuroanatomy and activation patterns between youth with conduct disorder and controls, neurochemical profiles also vary between groups. Individuals with conduct disorder are characterised as having reduced serotonin and cortisol levels (e.g. reduced hypothalamic-pituitary-adrenal (HPA) axis), as well as reduced autonomic nervous system (ANS) functioning. These reductions are associated with the inability to regulate mood and impulsive behaviours, weakened signals of anxiety and fear, and decreased self-esteem. Taken together, these findings may account for some of the variance in the psychological and behavioural patterns of youth with conduct disorder.

Intra-Individual Factors

Aside from findings related to neurological and neurochemical profiles of youth with conduct disorder, intraindividual factors such as genetics may also be relevant. Having a sibling or parent with conduct disorder increases the likelihood of having the disorder, with a heritability rate of .53. There also tends to be a stronger genetic link for individuals with childhood-onset compared to adolescent onset. In addition, youth with conduct disorder also exhibit polymorphism in the monoamine oxidase A gene, low resting heart rates, and increased testosterone.

Family and Peer Influences

Elements of the family and social environment may also play a role in the development and maintenance of conduct disorder. For instance, antisocial behaviour suggestive of conduct disorder is associated with single parent status, parental divorce, large family size, and the young age of mothers. However, these factors are difficult to tease apart from other demographic variables that are known to be linked with conduct disorder, including poverty and low socioeconomic status. Family functioning and parent-child interactions also play a substantial role in childhood aggression and conduct disorder, with low levels of parental involvement, inadequate supervision, and unpredictable discipline practices reinforcing youth’s defiant behaviours. Peer influences have also been related to the development of antisocial behaviour in youth, particularly peer rejection in childhood and association with deviant peers. Peer rejection is not only a marker of a number of externalizing disorders, but also a contributing factor for the continuity of the disorders over time. Hinshaw and Lee (2003) also explain that association with deviant peers has been thought to influence the development of conduct disorder in two ways: 1) a “selection” process whereby youth with aggressive characteristics choose deviant friends, and 2) a “facilitation” process whereby deviant peer networks bolster patterns of antisocial behaviour. In a separate study by Bonin and colleagues, parenting programmes were shown to positively affect child behaviour and reduce costs to the public sector.

Wider Contextual Factors

In addition to the individual and social factors associated with conduct disorder, research has highlighted the importance of environment and context in youth with antisocial behaviour. However, it is important to note that these are not static factors, but rather transactional in nature (e.g. individuals are influenced by and also influence their environment). For instance, neighbourhood safety and exposure to violence have been studied in conjunction with conduct disorder, but it is not simply the case that youth with aggressive tendencies reside in violent neighbourhoods. Transactional models propose that youth may resort to violence more often as a result of exposure to community violence, but their predisposition towards violence also contributes to neighbourhood climate.

Diagnosis

Conduct disorder is classified in the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM). It is diagnosed based on a prolonged pattern of antisocial behaviour such as serious violation of laws and social norms and rules in people younger than the age of 18. Similar criteria are used in those over the age of 18 for the diagnosis of antisocial personality disorder. No proposed revisions for the main criteria of conduct disorder exist in the DSM-5; there is a recommendation by the work group to add an additional specifier for callous and unemotional traits. According to DSM-5 criteria for conduct disorder, there are four categories that could be present in the child’s behaviour: aggression to people and animals, destruction of property, deceitfulness or theft, and serious violation of rules.

Almost all adolescents who have a substance use disorder have conduct disorder-like traits, but after successful treatment of the substance use disorder, about half of these adolescents no longer display conduct disorder-like symptoms. Therefore, it is important to exclude a substance-induced cause and instead address the substance use disorder prior to making a psychiatric diagnosis of conduct disorder.

Treatment

First-line treatment is psychotherapy based on behaviour modification and problem-solving skills. This treatment seeks to integrate individual, school, and family settings. Parent-management training can also be helpful. No medications have been FDA approved for Conduct Disorder, but Risperidone (a second-generation antipsychotic) has the most evidence to support its use for aggression in children who have not responded to behavioural and psychosocial interventions. Selective Serotonin Reuptake Inhibitors (SSRIs) are also sometimes used to treat irritability in these patients.

Prognosis

About 25-40% of youths diagnosed with conduct disorder qualify for a diagnosis of antisocial personality disorder when they reach adulthood. For those that do not develop ASPD, most still exhibit social dysfunction in adult life.

Epidemiology

Conduct disorder is estimated to affect 51.1 million people globally as of 2013. The percentage of children affected by conduct disorder is estimated to range from 1-10%. However, among incarcerated youth or youth in juvenile detention facilities, rates of conduct disorder are between 23% and 87%.

Sex Differences

The majority of research on conduct disorder suggests that there are a significantly greater number of males than females with the diagnosis, with some reports demonstrating a threefold to fourfold difference in prevalence. However, this difference may be somewhat biased by the diagnostic criteria which focus on more overt behaviours, such as aggression and fighting, which are more often exhibited by males. Females are more likely to be characterised by covert behaviours, such as stealing or running away. Moreover, conduct disorder in females is linked to several negative outcomes, such as antisocial personality disorder and early pregnancy, suggesting that sex differences in disruptive behaviours need to be more fully understood.

Females are more responsive to peer pressure including feelings of guilt than males.

Racial Differences

Research on racial or cultural differences on the prevalence or presentation of conduct disorder is limited. However, according to studies on American youth, it appears that African-American youth are more often diagnosed with conduct disorder, while Asian-American youth are about one-third as likely to develop conduct disorder when compared to White American youth. It has been widely theorised for decades that this disparity is due to unconscious bias in those who give the diagnosis.

What is Pharmacotherapy?

Published on by Andrew Marshall2 Comments

Introduction

Pharmacotherapy is therapy using pharmaceutical drugs, as distinguished from therapy using surgery (surgical therapy), radiation (radiation therapy), movement (physical therapy), or other modes. Among physicians, sometimes the term medical therapy refers specifically to pharmacotherapy as opposed to surgical or other therapy; for example, in oncology, medical oncology is thus distinguished from surgical oncology. Pharmacists are experts in pharmacotherapy and are responsible for ensuring the safe, appropriate, and economical use of pharmaceutical drugs.

Background

The skills required to function as a pharmacist require knowledge, training and experience in biomedical, pharmaceutical and clinical sciences. Pharmacology is the science that aims to continually improve pharmacotherapy. The pharmaceutical industry and academia use basic science, applied science, and translational science to create new pharmaceutical drugs.

As pharmacotherapy specialists and pharmacists have responsibility for direct patient care, often functioning as a member of a multidisciplinary team, and acting as the primary source of drug-related information for other healthcare professionals. A pharmacotherapy specialist is an individual who is specialised in administering and prescribing medication, and requires extensive academic knowledge in pharmacotherapy.

In the US, a pharmacist can gain Board Certification in the area of pharmacotherapy upon fulfilling eligibility requirements and passing a certification examination.

While pharmacists provide valuable information about medications for patients and healthcare professionals, they are not typically considered covered pharmacotherapy providers by insurance companies.

What is Depressive Disorder Not Otherwise Specified?

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Introduction

Depressive Disorder Not Otherwise Specified (DD-NOS) is designated by the code 311 in the DSM-IV for depressive disorders that are impairing but do not fit any of the officially specified diagnoses. According to the DSM-IV, DD-NOS encompasses “any depressive disorder that does not meet the criteria for a specific disorder.” In the DSM-5, it is called unspecified depressive disorder.

Refer to Dissociative Disorder Not Otherwise Specified (DDNOS).

Background

Examples of disorders in this category include those sometimes described as minor depressive disorder and recurrent brief depression.

“Depression” refers to a spectrum of disturbances in mood that vary from mild to severe and from short periods to constant illness. DD-NOS is diagnosed if a patients symptoms fail to meet the criteria more common depressive disorders such as major depressive disorder or dysthymia. Although DD-NOS shares similar symptoms to dysthymia, dysthymia is classified by a period of at least 2 years of constantly recurring depressed mood, where as DD-NOS is classified by much shorter periods of depressed moods.

For most people who suffer the condition, their life will be significantly affected. DD-NOS can make many aspects of a person’s daily life difficult to manage, inhibiting their ability to enjoy the things that used to make them happy. Sufferers of the disorder tend to isolate themselves from their friends and families, lose interest in some activities, and experience behavioural changes and sleeping disorders. Some sufferers also experience suicidal tendencies or suicide attempts. In addition to having these symptoms, a diagnosis of DD-NOS will only be made if the symptoms cause significant distress or impairment in social, occupational, or other important areas of functioning. For the diagnosis to be accurate, a psychiatrist is required to spend extensive time with the patient.

Symptoms of the disorder may arise due to several reasons. These include:

  • Distress due to medical conditions.
  • Environmental effects and situations.

However, the effects of drugs or medication or bereavement are not classified under the diagnosis.

A person will not be diagnosed with the condition if they have or have had any of the following: a major depressive episode, manic episode, mixed episode or hypomanic episode.

A diagnosis of the disorder will look like: “Depressive Disorder NOS 311”.

Concerns

Accurately assessing for a specific Depressive Disorder diagnosis requires an expenditure of time that is deemed unreasonable for most primary care physicians. For this reason, physicians often use this code as a proxy for a more thorough diagnosis. There is concern that this may lead to a “wastebasket” mindset for certain disorders. In addition reimbursement through Medicare may be lower for certain non specific diagnosis.

Treatment

It is possible for this disorder to progress over time. A patient suffering from the disorder can improve the condition with treatments. There are several types of therapies that may improve the condition, but depending on a patient’s experience of the disorder or the cause of the disorder, treatments will vary.

  • Psychotherapy including behaviour therapy, Gestalt therapy, Adlerian therapy, psychoanalytic therapy and existential therapy.
  • Pharmacotherapy through medications including antidepressants.

Book: Case Studies: Stahl’s Essential Psychopharmacology, Volume 02

Published on by Andrew Marshall1 Comment

Book Title:

Case Studies: Stahl’s Essential Psychopharmacology, Volume 02.

Author(s): Stephen M. Stahl.

Year: 2016.

Edition: First (1ed).

Publisher: Cambridge University Press.

Type(s): Paperback.

Synopsis:

Following the success of the first collection of Stahl’s Case Studies, published in 2011, we are pleased to present this completely new selection of clinical stories.

Designed with the distinctive user-friendly presentation readers have become accustomed to and making use of icons, questions/answers and tips, these cases address complex issues in an understandable way and with direct relevance to the everyday experience of clinicians.

Covering a wide-ranging and representative selection of clinical scenarios, each case is followed through the complete clinical encounter, from start to resolution, acknowledging all the complications, issues, decisions, twists and turns along the way.

The book is about living through the treatments that work, the treatments that fail, and the mistakes made along the journey. This is psychiatry in real life – these are the patients from your waiting room – this book will reassure, inform and guide better clinical decision making.

Book: Case Studies: Stahl’s Essential Psychopharmacology

Published on by Andrew Marshall1 Comment

Book Title:

Case Studies: Stahl’s Essential Psychopharmacology

Author(s): Stephen M. Stahl (Author), Debbi A. Morrisette (Editor), and Nancy Muntner (Illustrator).

Year: 2011.

Edition: First (1ed).

Publisher: Cambridge University Press.

Type(s): Paperback.

Synopsis:

Designed with the distinctive, user-friendly presentation Dr Stahl’s audience know and love, this new stream of Stahl books capitalise on Dr Stahl’s greatest strength – the ability to address complex issues in an understandable way and with direct relevance to the everyday experience of clinicians.

The book describes a wide-ranging and representative selection of clinical scenarios, making use of icons, questions/answers and tips. It follows these cases through the complete clinical encounter, from start to resolution, acknowledging all the complications, issues, decisions, twists and turns along the way.

The book is about living through the treatments that work, the treatments that fail, and the mistakes made along the journey. This is psychiatry in real life – these are the patients from your waiting room – this book will reassure, inform and guide better clinical decision making.

Find Volume 02 here.

Book: Pharmacotherapy: A Pathophysiologic Approach

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Book Title:

Pharmacotherapy: A Pathophysiologic Approach.

Author(s): Joseph Dipiro, Robert Talbert, Gary Yee, Gary Matzke, Barbara Wells, and L. Michael Posey.

Year: 2011.

Edition: Eighth (8th).

Publisher: McGraw-Hill Education.

Type(s): Hardcover and Paperback.

Synopsis:

The eighth edition will feature the addition of SI units throughout and an increased number of global examples and clinical questions.

Features:

  • Unparalleled guidance in the development of pharmaceutical care plans.
  • Full-colour presentation.
  • Key Concepts in each chapter.
  • Critical Presentation boxes summarise common disease signs and symptoms.
  • Clinical Controversies boxes examine complicated issues you face when providing drug therapy.
  • New material added to the online learning centre.
  • Expanded evidence-based recommendations.
  • Expanded coverage of timely issues such as palliative care and pain medicine.
  • Therapeutic recommendations in each disease-specific chapter.

Book: Beating OCD and Anxiety

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Book Title:

Beating OCD and Anxiety – 75 Tried and Tested Strategies for Sufferers and their Supporters.

Author(s): Helena Tarrant.

Year: 2020.

Edition: First (1st).

Publisher: Cherish Editions.

Type(s): Paperback and Kindle.

Synopsis:

Does anxiety impact on everything you do, leaving you unable to get through the day or with an inability to make decisions, no matter how small? Has it affected or even destroyed friendships and relationships? Or maybe you know or live with someone with these issues, and feel unable to help them?

Helena Tarrant gets it. She also understands why you may have struggled with text-heavy anxiety guides in the past. This book can help you to start a new fulfilling life, or help you provide invaluable support to someone you care about. The author has recovered from lifelong debilitating obsessive compulsive disorder and generalized anxiety disorder. This book shares the tried and tested techniques that she used to do it, based largely but not entirely on the methods and concepts behind cognitive behavioural therapy.

Written in accessible language, conveniently segmented and illustrated with over 100 original cartoons, the techniques are described clearly and concisely. Beating OCD and Anxiety knows you don’t want to read pages of complex theory on your quest for help.

In this book, Helena will show you how to get your life back.

Book: Anxiety and Depression in Children and Adolescents

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Book Title:

Anxiety and Depression in Children and Adolescents: Assessment, Intervention, and Prevention.

Author(s): Thomas J. Huberty..

Year: 2012.

Edition: First (1st).

Publisher: Springer.

Type(s): Hardcover and eBook.

Synopsis:

Although generally considered adult disorders, anxiety and depression are widespread among children and adolescents, affecting academic performance, social development, and long-term outcomes. They are also difficult to treat and, especially when they occur in tandem, tend to fly under the diagnostic radar.

Anxiety and Depression in Children and Adolescents offers a developmental psychology perspective for understanding and treating these complex disorders as they manifest in young people. Adding the school environment to well-known developmental contexts such as biology, genetics, social structures, and family, this significant volume provides a rich foundation for study and practice by analyzing the progression of pathology and the critical role of emotion regulation in anxiety disorders, depressive disorders, and in combination. Accurate diagnostic techniques, appropriate intervention methods, and empirically sound prevention strategies are given accessible, clinically relevant coverage. Illustrative case examples and an appendix of forms and checklists help make the book especially useful.

Featured in the text:

  • Developmental psychopathology of anxiety, anxiety disorders, depression, and mood disorders.
  • Differential diagnosis of the anxiety and depressive disorders.
  • Assessment measures for specific conditions.
  • Age-appropriate interventions for anxiety and depression, including CBT and pharmacotherapy.
  • Multitier school-based intervention and community programmes.
  • Building resilience through prevention.

Anxiety and Depression in Children and Adolescents is an essential reference for practitioners, researchers, and graduate students in school and clinical child psychology, mental health and school counselling, family therapy, psychiatry, social work, and education.