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What is Lamotrigine?

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Introduction

Lamotrigine, sold as the brand name Lamictal among others, is an anticonvulsant medication used to treat epilepsy and to delay or prevent the recurrence of depressive episodes in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut syndrome. In bipolar disorder, lamotrigine has not been shown to reliably treat acute depression; but for patients with bipolar disorder who are not currently symptomatic, it appears to be effective in reducing the risk of future episodes of depression.

Common side effects include nausea, sleepiness, headache, vomiting, trouble with coordination, and rash. Serious side effects include lack of red blood cells, increased risk of suicide, Stevens-Johnson syndrome, and allergic reactions. Concerns exist that use during pregnancy or breastfeeding may result in harm. Lamotrigine is a phenyltriazine, making it chemically different from other anticonvulsants. Its mechanism of action is not clear, but it appears to inhibit release of excitatory neurotransmitters via voltage-sensitive sodium channels in neurons.

Lamotrigine was first marketed in the United Kingdom in 1991, and approved for use in the United States in 1994. It is on the World Health Organization’s List of Essential Medicines. In 2019, it was the 71st most commonly prescribed medication in the United States, with more than 10 million prescriptions.

Brief History

  • 1991 – Lamotrigine is first used in the United Kingdom as an anticonvulsant medication.
  • December 1994 – Lamotrigine was first approved for use in the United States and, that for the treatment of partial seizures.
  • August 1998 – For use as adjunctive treatment of Lennox-Gastaut syndrome in paediatric and adult patients, new dosage form: chewable dispersible tablets.
  • December 1998 – For use as monotherapy for treatment of partial seizures in adult patients when converting from a single enzyme-inducing anticonvulsant drug.
  • January 2003 – For use as adjunctive therapy for partial seizures in paediatric patients as young as two years of age.
  • June 2003 – Approved for maintenance treatment of Bipolar II disorder; the first such medication since lithium.
  • January 2004 – For use as monotherapy for treatment of partial seizures in adult patients when converting from the anti-epileptic drug valproate (including valproic acid).

Medical Uses

Epilepsy

Lamotrigine is considered a first-line drug for primary generalized tonic-clonic seizures (includes simple partial, complex partial, and secondarily generalized seizures such as focal-onset tonic-clonic seizures). It is also used as an alternative or adjuvant medication for partial seizures, such as absence seizure, myoclonic seizure, and atonic seizures. A 2020 review on the use of Lamotrigine as an add-on therapy for drug resistant generalized tonic-clonic seizures was unable to come to conclusions to inform clinical practice. Although low-certainty evidence suggest that it reduces generalised tonic-clonic seizures by 50% the level of uncertainty indicates that the actual findings could be significantly different. Another 2020 Cochrane review examining the use of lamotrigine as an add-on therapy for drug-resistant focal epilepsy found it to be effective for reducing seizure frequency and was well tolerated.

Lennox-Gastaut Syndrome

Lamotrigine is one of a small number of FDA-approved therapies for the form of epilepsy known as Lennox-Gastaut syndrome. It reduces the frequency of LGS seizures, and is one of two medications known to decrease the severity of drop attacks. Combination with valproate is common, but this increases the risk of lamotrigine-induced rash, and necessitates reduced dosing due to the interaction of these drugs.

Bipolar Disorder

Lamotrigine is approved in the US for maintenance treatment of bipolar I disorder and bipolar II disorder. While the anticonvulsants carbamazepine and valproate are predominantly antimanics, lamotrigine has demonstrated efficacy only in preventing or reducing the risk of recurrent depressive episodes of bipolar disorder. The drug seems ineffective in the treatment of current rapid-cycling, acute mania, or acute depression in bipolar disorder.

Lamotrigine has not demonstrated clear efficacy in treating acute mood episodes, either mania or depression. It has not demonstrated effectiveness in treating acute mania, and there is controversy regarding the drug’s effectiveness in treating acute bipolar depression. A paper written in 2008 by Nassir et al. reviewed evidence from trials that were unpublished and not referenced in the 2002 APA guidelines, and it concludes that lamotrigine has “very limited, if any, efficacy in the treatment of acute bipolar depression”. A 2008 paper by Calabrese et al. examined much of the same data, and found that in five placebo-controlled studies, lamotrigine did not significantly differ from placebo in the treatment of bipolar depression. However, in a meta-analysis of these studies conducted in 2008, Geddes, Calabrese and Goodwin found that lamotrigine was effective in individuals with bipolar depression, with a number needed to treat (NNT) of 11, or 7 in severe depression.

A 2013 review about lamotrigine concluded that it is recommended in bipolar maintenance when depression is prominent and that more research is needed in regard to its role in the treatment of acute bipolar depression and unipolar depression. No information to recommend its use in other psychiatric disorders was found.

Schizophrenia

Lamotrigine, as a monotherapy, is not substantially effective against schizophrenia. However; various publications and textbooks have expressed that lamotrigine could be added to clozapine as augmentation therapy against partial or non-responding schizophrenic patients. Patients had statistically significant improvements in positive, negative and affective symptoms. Lamotrigine does not have a statistically significant effect with antipsychotics other than clozapine, such as: olanzapine, risperidone, haloperidol, zuclopenthixol, etc.

Other Uses

Off-label uses include the treatment of peripheral neuropathy, trigeminal neuralgia, cluster headaches, migraines, visual snow, and reducing neuropathic pain, although a systematic review conducted in 2013 concluded that well-designed clinical trials have shown no benefit for lamotrigine in neuropathic pain. Off-label psychiatric usage includes the treatment of treatment-resistant obsessive-compulsive disorder, depersonalisation disorder, hallucinogen persisting perception disorder, schizoaffective disorder, and borderline personality disorder.

It has not been shown to be useful in post-traumatic stress disorder.

Side Effects

Lamotrigine prescribing information has a black box warning about life-threatening skin reactions, including Stevens-Johnson syndrome (SJS), DRESS syndrome, and toxic epidermal necrolysis (TEN). The manufacturer states that nearly all cases appear in the first two to eight weeks of therapy. Patients should seek medical attention for any unexpected skin rash, as its presence is an indication of a possible serious or even deadly side effect of the drug. Not all rashes that occur while taking lamotrigine progress to SJS or TEN. Between 5 and 10% of patients will develop a rash, but only one in a thousand patients will develop a serious rash. Rash and other skin reactions are more common in children, so this medication is often reserved for adults. For patients whose lamotrigine has been stopped after development of a rash, rechallenge with lamotrigine is also a viable option. However, it is not applicable for very serious cases. The incidence of these eruptions increases in patients who are currently on, or recently discontinued a valproate-type anticonvulsant drug, as these medications interact in such a way that the clearance of both is decreased and the effective dose of lamotrigine is increased.

Side effects such as rash, fever, and fatigue are very serious, as they may indicate incipient SJS, TEN, DRESS syndrome, or aseptic meningitis. Other side effects include loss of balance or coordination, double vision, crossed eyes, pupil constriction, blurred vision, dizziness and lack of coordination, drowsiness, insomnia, anxiety, vivid dreams or nightmares, dry mouth, mouth ulcers, memory problems, mood changes, itchiness, runny nose, cough, nausea, indigestion, abdominal pain, weight loss, missed or painful menstrual periods, and vaginitis. The side-effects profile varies for different patient populations. Overall adverse effects in treatment are similar between men, women, geriatric, paediatric and racial groups.

Lamotrigine has been associated with a decrease in white blood cell count (leukopenia). Lamotrigine does not prolong QT/QTc in TQT studies in healthy subjects.

In people taking antipsychotics, cases of lamotrigine-precipitated neuroleptic malignant syndrome have been reported.

In 2018, the FDA required a new warning for the risk of hemophagocytic lymphohistiocytosis. This reaction can occur between days to weeks after starting the treatment.

Women

Women are more likely than men to have side effects. This is the opposite of most other anticonvulsants.

Some evidence shows interactions between lamotrigine and female hormones, which can be of particular concern for women on oestrogen-containing hormonal contraceptives. Ethinylestradiol, an ingredient of such contraceptives, has been shown to decrease serum levels of lamotrigine. Women starting an oestrogen-containing oral contraceptive may need to increase the dosage of lamotrigine to maintain its level of efficacy. Likewise, women may experience an increase in lamotrigine side effects upon discontinuation of birth control pills. This may include the “pill-free” week where lamotrigine serum levels have been shown to increase twofold.

Pregnancy and Breastfeeding

Many studies have found no association between lamotrigine exposure in utero and birth defects, while those that have found an association have found only slight associations with minor malformations such as cleft palates. Review studies have found that overall rates of congenital malformations in infants exposed to lamotrigine in utero are relatively low (1-4%), which is similar to the rate of malformations in the general population. It is known that lamotrigine is a weak inhibitor of human dihydrofolate reductase (DHFR) and other, more powerful, human DHFR inhibitors such as methotrexate are known to be teratogenic.

Lamotrigine is expressed in breast milk; the manufacturer does not recommend breastfeeding during treatment. However, recent studies suggest that lamotrigine is safe to use while breastfeeding. A frequently updated review of scientific literature rates lamotrigine as L3: moderately safe.

Other Types of Effects

Lamotrigine binds to melanin-containing tissues such as the iris of the eye or melanin-rich skin. The long-term consequences of this are unknown.

GlaxoSmithKline investigated lamotrigine for the treatment of ADHD with inconclusive results. No detrimental effects on cognitive function were observed; however, the only statistical improvement in core ADHD symptoms was an improvement on a Paced Auditory Serial Addition Test (PASAT) that measures auditory processing speed and calculation ability. Another study reported that lamotrigine might be a safe and effective treatment option for adult ADHD comorbid with bipolar and recurrent depression.

Lamotrigine is known to affect sleep. Studies with small numbers of patients (10-15) reported that lamotrigine increases the duration of REM sleep, decreases the number of phase shifts, and decreases the duration of slow-wave sleep, and that there was no effect on vigilance, daytime somnolence and cognitive function. However, a retrospective study of 109 patients’ medical records found that 6.7% of patients experienced an “alerting effect” resulting in intolerable insomnia, for which the treatment had to be discontinued.

Lamotrigine can induce a type of seizure known as a myoclonic jerk, which tends to happen soon after the use of the medication. When used in the treatment of myoclonic epilepsies such as juvenile myoclonic epilepsy, lower doses (and lower plasma levels) are usually needed, as even moderate doses of this drug can induce seizures, including tonic-clonic seizures, which can develop into status epilepticus, which is a medical emergency. It can also cause myoclonic status epilepticus.

In overdose, lamotrigine can cause uncontrolled seizures in most people. Reported results in overdoses involving up to 15 g include increased seizures, coma, and death.

Pharmacology

Mechanism of Action

Lamotrigine is a member of the sodium channel blocking class of antiepileptic drugs. This may suppress the release of glutamate and aspartate, two dominant excitatory neurotransmitters in the central nervous system. It is generally accepted to be a member of the sodium channel blocking class of antiepileptic drugs, but it could have additional actions, since it has a broader spectrum of action than other sodium channel antiepileptic drugs such as phenytoin and is effective in the treatment of the depressed phase of bipolar disorder, whereas other sodium channel-blocking antiepileptic drugs are not, possibly on account of its sigma receptor activity. In addition, lamotrigine shares few side effects with other, unrelated anticonvulsants known to inhibit sodium channels, which further emphasizes its unique properties.

It is a triazine derivate that inhibits voltage-sensitive sodium channels, leading to stabilisation of neuronal membranes. It also blocks L-, N-, and P-type calcium channels and weakly inhibits the serotonin 5-HT3 receptor. These actions are thought to inhibit release of glutamate at cortical projections in the ventral striatum limbic areas, and its neuroprotective and anti-glutamatergic effects have been pointed out as promising contributors to its mood stabilising activity. Observations that lamotrigine reduced γ-aminobutyric acid (GABA) A receptor-mediated neurotransmission in rat amygdala, suggest that a GABAergic mechanism may also be involved. It appears that lamotrigine does not increase GABA blood levels in humans.

Lamotrigine does not have pronounced effects on any of the usual neurotransmitter receptors that anticonvulsants affect (adrenergic, dopamine D1 and D2, muscarinic, GABA, histaminergic H1, serotonin 5-HT2, and N-methyl-D-aspartate). Inhibitory effects on 5-HT, norepinephrine, and dopamine transporters are weak. Lamotrigine is a weak inhibitor of dihydrofolate reductase, but whether this effect is sufficient to contribute to a mechanism of action or increases risk to the foetus during pregnancy is not known. Early studies of lamotrigine’s mechanism of action examined its effects on the release of endogenous amino acids from rat cerebral cortex slices in vitro. As is the case for antiepileptic drugs that act on voltage-dependent sodium channels, lamotrigine thereby inhibits the release of glutamate and aspartate, which is evoked by the sodium-channel activator veratrine, and was less effective in the inhibition of acetylcholine or GABA release. At high concentrations, it had no effect on spontaneous or potassium-evoked amino acid release.

These studies suggested that lamotrigine acts presynaptically on voltage-gated sodium channels to decrease glutamate release. Several electrophysiological studies have investigated the effects of lamotrigine on voltage-gated sodium channels. For example, lamotrigine blocked sustained repetitive firing in cultured mouse spinal cord neurons in a concentration-dependent manner, at concentrations that are therapeutically relevant in the treatment of human seizures. In cultured hippocampal neurons, lamotrigine reduced sodium currents in a voltage-dependent manner, and at depolarised potentials showed a small frequency-dependent inhibition. These and a variety of other results indicate that the antiepileptic effect of lamotrigine, like those of phenytoin and carbamazepine, is at least in part due to use- and voltage-dependent modulation of fast voltage-dependent sodium currents. However, lamotrigine has a broader clinical spectrum of activity than phenytoin and carbamazepine and is recognised to be protective against generalised absence epilepsy and other generalised epilepsy syndromes, including primary generalised tonic-clonic seizures, juvenile myoclonic epilepsy, and Lennox-Gastaut syndrome.

The basis for this broader spectrum of activity of lamotrigine is unknown, but could relate to actions of the drug on voltage-gated calcium channels. Lamotrigine blocks T-type calcium channels weakly, if at all. However, it does inhibit native and recombinant high voltage–gated calcium channels (N- and P/Q/R-types) at therapeutic concentrations. Whether this activity on calcium channels accounts for lamotrigine’s broader clinical spectrum of activity in comparison with phenytoin and carbamazepine remains to be determined.

It antagonises these receptors with the following IC50 values:

  • 5-HT3, IC50 = 18 μM
  • σ receptors, IC50 = 145 μM

Pharmacokinetics

The pharmacokinetics of lamotrigine follow first-order kinetics, with a half-life of 29 hours and volume of distribution of 1.36 L/kg. Lamotrigine is rapidly and completely absorbed after oral administration. Its absolute bioavailability is 98% and its plasma Cmax occurs from 1.4 to 4.8 hours. Available data indicate that its bioavailability is not affected by food. Estimate of the mean apparent volume of distribution of lamotrigine following oral administration ranges from 0.9 to 1.3 L/kg. This is independent of dose and is similar following single and multiple doses in both patients with epilepsy and in healthy volunteers.

Lamotrigine is inactivated by glucuronidation in the liver. Lamotrigine is metabolised predominantly by glucuronic acid conjugation. Its major metabolite is an inactive 2-n-glucuronide conjugate.

Lamotrigine has fewer drug interactions than many anticonvulsant drugs, although pharmacokinetic interactions with carbamazepine, phenytoin and other hepatic enzyme inducing medications may shorten half-life. Dose adjustments should be made on clinical response, but monitoring may be of benefit in assessing compliance.

The capacity of available tests to detect potentially adverse consequences of melanin binding is unknown. Clinical trials excluded subtle effects and optimal duration of treatment. There are no specific recommendations for periodic ophthalmological monitoring. Lamotrigine binds to the eye and melanin-containing tissues which can accumulate over time and may cause toxicity. Prescribers should be aware of the possibility of long-term ophthalmologic effects and base treatment on clinical response. Patient compliance should be periodically reassessed with lab and medical testing of liver and kidney function to monitor progress or side effects.

Society and Culture

Brand Names

Lamotrigine was originally brought to market by GlaxoSmithKline, trademarked as Lamictal; it is also available in generic form under many brand names worldwide.

What is a Paced Auditory Serial Addition Test?

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Introduction

Paced Auditory Serial Addition Test (PASAT) is a neuropsychological test used to assess capacity and rate of information processing and sustained and divided attention.

Background

Originally the test was known as the Paced Auditory Serial Addition Task (PASAT). The subjects are given in the version used as part of the Multiple Sclerosis Functional Composite a number every 3 seconds and are asked to add the number they just heard with the number they heard before. This is a challenging task that involves working memory, attention and arithmetic capabilities. Versions with numbers presented every 2 seconds are also available. The original version presented the numbers every 2.4 seconds with 0.4 decrements for subsequent trials. The PASAT was originally developed for use in evaluating patients with head injury. The advantage in this population was supposed to be minimal practice effects. This test has been widely used in other conditions besides traumatic brain injury.

Multiple Sclerosis

It has become widely used in the testing of patients with multiple sclerosis as patients with this disease frequently have an impaired performance on this test. The PASAT was included in the Multiple Sclerosis Functional Composite as a cognitive measure. However, the use of the PASAT in clinical trials in MS it has shown to be problematic as there are significant practice effects over repeated measures; typically the effect of treatment is reflected by a larger improvement on the test compared to the control group.

What is the International Association for Suicide Prevention?

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Introduction

The International Association for Suicide Prevention (IASP) is an international suicide prevention organisation.

Background

Founded by Erwin Ringel and Norman Farberow in 1960, IASP, which is in an official relationship with the World Health Organisation (WHO), is dedicated to preventing suicidal behaviour and providing a forum for mental health professionals, crisis workers, suicide survivors and other people in one way or another affected by suicidal behaviour. The organisation now consists of professionals and volunteers from over 50 countries worldwide.

The IASP also co-sponsors, with the WHO, World Suicide Prevention Day on 10 September every year.

IASP Congresses

The IASP holds international congresses every two years. XXIX World Congress of the IASP will be organised in Kuching (Malaysia) in 2017.

Past Congresses

  • 2021 Queensland, Australia.
  • 2019 Derry-Londonderry, Northern Ireland.
  • 2017 Kucjing, Malaysia.
  • 2015 Montreal, Canada.
  • 2013 Oslo, Norway.
  • 2011 Beijing, China.
  • 2009 Montevideo, Uruguay.
  • 2007 Killarney, Ireland.
  • 2005 Durban, South Africa.
  • 2003 Stockholm, Sweden.
  • 2001 Chennai, India.
  • 1999 Athens, Greece.
  • 1997 Adelaide, Australia.
  • 1995 Venice, Italy.
  • 1993 Montreal Canada.
  • 1991 Hamburg, Germany.
  • 1989 Brussels, Belgium.
  • 1987 San Francisco, US.
  • 1985 Vienna, Austria.
  • 1983 Caracas, Venezuela.
  • 1981 Paris, France.
  • 1979 Ottawa, Canada.
  • 1977 Helsinki, Finland.
  • 1975 Jerusalem, Israel.
  • 1973 Amsterdam, Netherlands.
  • 1971 Mexico City, Mexico.
  • 1969 London, England.
  • 1967 Los Angeles, US.
  • 1965 Basel, Switzerland.
  • 1963 Copenhagen, Denmark.
  • 1960 Vienna, Austria.

Awards

The IASP provides awards for those who have contributed in a significant way to the furthering of the aims of the Association. Awards are presented at the IASP biennial conference.

The Stengel Research Award has been provided since 1977 and is named in honour of Professor Erwin Stengel, one of the founders of the IASP. This award is for outstanding research in the field of suicidology, and nominations can be made by any member of IASP.

The Ringel Service Award was instituted in 1995 and honours Professor Erwin Ringel, the founding President of the Association. This award is for distinguished service in the field of suicidology, and nominations can be made by National Representatives of IASP.

The Farberow Award was introduced in 1997 in recognition of Professor Norman Farberow, a founding member and driving force behind the IASP. This award is for a person who has contributed significantly in the field of work with survivors of suicide, and nominations can be made by any IASP member.

The De Leo Fund Award honours the memory of Nicola and Vittorio, the children of Professor Diego De Leo, IASP Past President. The Award is offered to distinguished scholars in recognition of their outstanding research on suicidal behaviours carried out in developing countries.

Journal

The Association’s journal, Crisis – The Journal of Crisis Intervention and Suicide Prevention, has been published since 1980.

Website

http://www.iasp.info/

On This Day … 25 October

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People (Births)

  • 1918 – David Ausubel, American psychologist (d. 2008).
  • 1927 – Lawrence Kohlberg, American psychologist and author (d. 1987).
  • 1977 – Birgit Prinz, German footballer and psychologist.

People (Deaths)

  • 1826 – Philippe Pinel, French physician and psychiatrist (b. 1745).

David Ausubel

David Paul Ausubel (25 October 1918 to 09 July 2008) was an American psychologist. His most significant contribution to the fields of educational psychology, cognitive science, and science education learning was on the development and research on “advance organizers” since 1960.

He studied at the University of Pennsylvania where he graduated with honors in 1939, receiving a bachelor’s degree majoring in psychology. Ausubel later graduated from medical school in 1943 at Middlesex University where he went on to complete a rotating internship at Gouverneur Hospital, located in the lower east side of Manhattan, New York. Following his military service with the US Public Health Service, Ausubel earned his M.A. and Ph.D. in developmental psychology from Columbia University in 1950. He continued to hold a series of professorships at several schools of education.

In 1973, Ausubel retired from academic life and devoted himself to his psychiatric practice. During his psychiatric practice, Ausubel published many books as well as articles in psychiatric and psychological journals. In 1976, he received the Thorndike Award from the American Psychological Association for “Distinguished Psychological Contributions to Education”.

Lawrence Kohlberg

Lawrence Kohlberg (25 October 1927 to 09 January 1987) was an American psychologist best known for his theory of stages of moral development.

He served as a professor in the Psychology Department at the University of Chicago and at the Graduate School of Education at Harvard University. Even though it was considered unusual in his era, he decided to study the topic of moral judgment, extending Jean Piaget’s account of children’s moral development from twenty-five years earlier. In fact, it took Kohlberg five years before he was able to publish an article based on his views. Kohlberg’s work reflected and extended not only Piaget’s findings but also the theories of philosophers George Herbert Mead and James Mark Baldwin. At the same time he was creating a new field within psychology: “moral development”.

In an empirical study using six criteria, such as citations and recognition, Kohlberg was found to be the 30th most eminent psychologist of the 20th century.

Birgit Prinz

Birgit Prinz (born 25 October 1977) is a German retired footballer, two-time FIFA Women’s World Cup champion and three-time FIFA World Player of the Year.

In addition to the German national team, Prinz played for 1. FFC Frankfurt in the Frauen-Bundesliga as well as the Carolina Courage in the Women’s United Soccer Association (WUSA), the first professional women’s league in the United States. Prinz remains one of the game’s most prolific strikers and is the second FIFA Women’s World Cup all-time leading scorer with 14 goals (second only to Marta from Brazil). On 12 August 2011, she announced the end of her active career.

She currently works as a sport psychologist for the men’s and women’s teams of 1. Bundesliga club TSG 1899 Hoffenheim.

Philippe Pinel

Philippe Pinel (20 April 1745 to 25 October 1826) was a French physician, precursor of psychiatry and incidentally a zoologist. He was instrumental in the development of a more humane psychological approach to the custody and care of psychiatric patients, referred to today as moral therapy. He worked for the abolition of the shackling of mental patients by chains and, more generally, for the humanisation of their treatment. He also made notable contributions to the classification of mental disorders and has been described by some as “the father of modern psychiatry”.

After the French Revolution, Dr. Pinel changed the way we look at the crazy (or “aliénés”, “alienated” in English) by claiming that they can be understood and cured. An 1809 description of a case that Pinel recorded in the second edition of his textbook on insanity is regarded by some as the earliest evidence for the existence of the form of mental disorder later known as dementia praecox or schizophrenia, although Emil Kraepelin is generally accredited with its first conceptualisation.

“Father of modern psychiatry”, he was credited with the first classification of mental illnesses. He had a great influence on psychiatry and the treatment of the alienated in Europe and the United States.

On This Day … 24 October

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People (Births)

  • 1959 – Ruth Perednik, English-Israeli psychologist and academic.

Ruth Perednik

Ruth Perednik (née Kestenbaum, Hebrew: רות פרדניק‎; born in London, 24 October 1959) is an English-born Israeli psychologist, pioneer in the field of selective mutism.

Biography

Ruth Perednik graduated from University College London (1983) and the Institute of Education, University of London (1984) and the Hebrew University of Jerusalem (Educational Psychology, 2002). Her thesis in England was on The Relation Between Mothers’ Attentiveness to Toddlers and Child’s Attachment to Mother and in Israel she completed her thesis on Selective Mutism in Immigrant Families, under the supervision of Professor Yoel Elizur, with a grant from the Martin and Vivian Levin Centre for the Development of the Child and Adolescent. Ruth Perednik taught at the Lincoln School, and at the Yehuda Halevi Teacher’s Training College, Argentina (1986-1987), where she lectured on Educational Psychology. She resides in the outskirts of Jerusalem with her husband, Gustavo Perednik; they have five children.

Expertise

Ruth Perednik has been specialising in the treatment of children with Selective Mutism and other anxiety disorders over the past 20 years. She has developed a treatment method for Selective Mutism based on cognitive behavioural techniques, in the framework of her work in the Jerusalem Psychological Services in the Jerusalem Municipality. Perednik heads a treatment clinic for children with Selective Mutism. She lectures and trains parents and therapists in Europe, the Americas and Asia. She has developed a Selective Mutism treatment manual which has been published in English and Chinese. She also published a Hebrew language treatment manual together with Professor Yoel Elitzur, of the Hebrew University.

The innovative element of Perednik’s treatment method is treating the child or teen in his natural environment (home and school sessions), and not in a clinic setting, since this is where the symptoms of the selective mutism hit hard and must be alleviated. This was considered iconoclastic when Perednik first published her treatment method, yet it has become generally accepted, and is the treatment of choice in several international selective mutism treatment centres. Perednik advocates for accountability of therapists when treating children, so that evidence-based interventions are the treatments of choice, facilitating effective therapy.

What is Flunitrazepam?

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Introduction

Flunitrazepam, also known as Rohypnol among other names, is a benzodiazepine used to treat severe insomnia and assist with anaesthesia.

As with other hypnotics, flunitrazepam has been advised to be prescribed only for short-term use or by those with chronic insomnia on an occasional basis. It is said to be 10 times as potent as diazepam.

It was patented in 1962 and came into medical use in 1974. Flunitrazepam, nicknamed “roofies”, is widely known for its use as a date rape drug.

Brief History

Flunitrazepam was discovered at Roche as part of the benzodiazepine work led by Leo Sternbach; the patent application was filed in 1962 and it was first marketed in 1974.

Due to use of the drug for date rape and recreation, in 1998 Roche modified the formulation to give lower doses, make it less soluble, and add a blue dye for easier detection in drinks. It was never marketed in the United States, and by 2016 had been withdrawn from the markets in Spain, France, Norway, Germany, and the United Kingdom.

Use

In countries where this drug is used, it is used for treatment of severe cases of sleeping problems, and in some countries as a preanesthetic agent. These were also the uses for which it was originally studied.

It has also been administered as a concurrent dose for patients that are taking ketamine. Rohypnol lowers the side effects of the anaesthetic (ketamine), resulting in less confusion in awakening states, less negative influence on pulse rate, and fewer fluctuations in blood pressure.

It has also been shown to have therapeutic use in polysubstance use when combined with anaesthetics, opioids, ethanol, cocaine, and methamphetamine.

Adverse Effects

Adverse effects of flunitrazepam include dependency, both physical and psychological; reduced sleep quality resulting in somnolence; and overdose, resulting in excessive sedation, impairment of balance and speech, respiratory depression or coma, and possibly death. Because of the latter, flunitrazepam is commonly used in suicide. When used in late pregnancy, it might cause hypotonia of the foetus.

Dependence

Flunitrazepam, as with other benzodiazepines, can lead to drug dependence. Discontinuation may result in benzodiazepine withdrawal syndrome, characterised by seizures, psychosis, insomnia, and anxiety. Rebound insomnia, worse than baseline insomnia, typically occurs after discontinuation of flunitrazepam even from short-term single nightly dose therapy.

Paradoxical Effects

Flunitrazepam may cause a paradoxical reaction in some individuals, including anxiety, aggressiveness, agitation, confusion, disinhibition, loss of impulse control, talkativeness, violent behaviour, and even convulsions. Paradoxical adverse effects may even lead to criminal behaviour.

Hypotonia

Benzodiazepines such as flunitrazepam are lipophilic and rapidly penetrate membranes and, therefore, rapidly cross over into the placenta with significant uptake of the drug. Use of benzodiazepines including flunitrazepam in late pregnancy, especially high doses, may result in hypotonia, also known as floppy baby syndrome.

Other

Flunitrazepam impairs cognitive functions. This may appear as lack of concentration, confusion and anterograde amnesia – the inability to create memories while under the influence. It can be described as a hangover-like effect which can persist to the next day. It also impairs psychomotor functions similar to other benzodiazepines and nonbenzodiazepine hypnotic drugs; falls and hip fractures were frequently reported. The combination with alcohol increases these impairments. Partial, but incomplete tolerance develops to these impairments.

Other adverse effects include:

  • Slurred speech.
  • Gastrointestinal disturbances, lasting 12 or more hours.
  • Vomiting.
  • Respiratory depression in higher doses.

Special Precautions

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, in alcohol- or drug-dependent individuals, and in individuals with comorbid psychiatric disorders.

Impairment of driving skills with a resultant increased risk of road traffic accidents is probably the most important adverse effect. This side-effect is not unique to flunitrazepam but also occurs with other hypnotic drugs. Flunitrazepam seems to have a particularly high risk of road traffic accidents compared to other hypnotic drugs. Extreme caution should be exercised by drivers after taking flunitrazepam.

Interactions

The use of flunitrazepam in combination with alcoholic beverages synergizes the adverse effects, and can lead to toxicity and death.

Overdose

Refer to Benzodiazepine Overdose.

Flunitrazepam is a drug that is frequently involved in drug intoxication, including overdose. Overdose of flunitrazepam may result in excessive sedation, or impairment of balance or speech. This may progress in severe overdoses to respiratory depression or coma and possibly death. The risk of overdose is increased if flunitrazepam is taken in combination with CNS depressants such as ethanol (alcohol) and opioids. Flunitrazepam overdose responds to the GABAA receptor antagonist flumazenil, which thus can be used as a treatment.

Detection

As of 2016, blood tests can identify flunitrazepam at concentrations of as low as 4 nanograms per millilitre; the elimination half life of the drug is 11-25 hours. For urine samples, metabolites can be identified for 60 hours to 28 days, depending on the dose and analytical method used. Hair and saliva can also be analysed; hair is useful when a long time has transpired since ingestion, and saliva for workplace drug tests.

Flunitrazepam can be measured in blood or plasma to confirm a diagnosis of poisoning in hospitalised patients, provide evidence in an impaired driving arrest, or assist in a medicolegal death investigation. Blood or plasma flunitrazepam concentrations are usually in a range of 5-20 μg/L in persons receiving the drug therapeutically as a nighttime hypnotic, 10-50 μg/L in those arrested for impaired driving and 100-1000 μg/L in victims of acute fatal overdosage. Urine is often the preferred specimen for routine substance use monitoring purposes. The presence of 7-aminoflunitrazepam, a pharmacologically-active metabolite and in vitro degradation product, is useful for confirmation of flunitrazepam ingestion. In postmortem specimens, the parent drug may have been entirely degraded over time to 7-aminoflunitrazepam. Other metabolites include desmethylflunitrazepam and 3-hydroxydesmethylflunitrazepam.

Pharmacology

The main pharmacological effects of flunitrazepam are the enhancement of GABA, an inhibitory neurotransmitter, at various GABA receptors.

While 80% of flunitrazepam that is taken orally is absorbed, bioavailability in suppository form is closer to 50%.

Flunitrazepam has a long half-life of 18-26 hours, which means that flunitrazepam’s effects after nighttime administration persist throughout the next day. This is due to the production of active metabolites. These metabolites further increase the duration of drug action compared to benzodiazepines that produce nonactive metabolites.

Flunitrazepam is lipophilic and is metabolised by the liver via oxidative pathways. The enzyme CYP3A4 is the main enzyme in its phase 1 metabolism in human liver microsomes.

Chemistry

Flunitrazepam is classed as a nitro-benzodiazepine. It is the fluorinated N-methyl derivative of nitrazepam. Other nitro-benzodiazepines include nitrazepam (the parent compound), nimetazepam (methylamino derivative) and clonazepam (2ʹ-chlorinated derivative).

Society and Culture

Recreational and Illegal Uses

Recreational Use

A 1989 article in the European Journal of Clinical Pharmacology reports that benzodiazepines accounted for 52% of prescription forgeries, suggesting that benzodiazepines was a major prescription drug class of abuse. Nitrazepam accounted for 13% of forged prescriptions.

Flunitrazepam and other sedative hypnotic drugs are detected frequently in cases of people suspected of driving under the influence of drugs. Other benzodiazepines and nonbenzodiazepines (anxiolytic or hypnotic) such as zolpidem and zopiclone (as well as cyclopyrrolones, imidazopyridines, and pyrazolopyrimidines) are also found in high numbers of suspected drugged drivers. Many drivers have blood levels far exceeding the therapeutic dose range, suggesting a high degree of potential for addiction for benzodiazepines and similar drugs.

Suicide

In studies in Sweden, flunitrazepam was the second most common drug used in suicides, being found in about 16% of cases. In a retrospective Swedish study of 1,587 deaths, in 159 cases benzodiazepines were found. In suicides when benzodiazepines were implicated, the benzodiazepines flunitrazepam and nitrazepam were occurring in significantly higher concentrations, compared to natural deaths. In 4 of the 159 cases, where benzodiazepines were found, benzodiazepines alone were the only cause of death. It was concluded that flunitrazepam and nitrazepam might be more toxic than other benzodiazepines.

Drug-Facilitated Sexual Assault

Flunitrazepam is known to induce anterograde amnesia in sufficient doses; individuals are unable to remember certain events that they experienced while under the influence of the drug, which complicates investigations. This effect could be particularly dangerous if flunitrazepam is used to aid in the commission of sexual assault; victims may be unable to clearly recall the assault, the assailant, or the events surrounding the assault.

While use of flunitrazepam in sexual assault has been prominent in the media, as of 2015 appears to be fairly rare, and use of alcohol and other benzodiazepine drugs in date rape appears to be a larger but underreported problem.

Drug-Facilitated Robbery

In the United Kingdom, the use of flunitrazepam and other “date rape” drugs have also been connected to stealing from sedated victims. An activist quoted by a British newspaper estimated that up to 2,000 individuals are robbed each year after being spiked with powerful sedatives, making drug-assisted robbery a more commonly reported problem than drug-assisted rape.

Regional Use

Flunitrazepam is a Schedule III drug under the international Convention on Psychotropic Substances of 1971.

  • In Australia, as of 2013 the drug was authorised for prescribing for severe cases of insomnia but was restricted as a Schedule 8 medicine.
  • In France, as of 2016 flunitrazepam was not marketed.
  • In Germany, as of 2016 flunitrazepam is an Anlage III Betäubungsmittel (controlled substance which is allowed to be marketed and prescribed by physicians under specific provisions) and is available on a special narcotic drug prescription as the Rohypnol 1 mg film-coated tablets and several generic preparations (November 2016).
  • In Ireland, flunitrazepam is a Schedule 3 controlled substance with strict restrictions.
  • In Japan, flunitrazepam is marketed by Japanese pharmaceutical company Chugai under the trade name Rohypnol and is indicated for the treatment of insomnia as well as used for preanesthetic medication.
  • In Mexico, Rohypnol is legally available and approved for medical use.
  • In Norway, on 01 January 2003, flunitrazepam was moved up one level in the schedule of controlled drugs and, on 01 August 2004, the manufacturer Roche removed Rohypnol from the market there altogether.
  • In South Africa, Rohypnol is classified as a Schedule 6 drug. It is available by prescription only, and restricted to 1 mg doses.
  • In Iceland, Flunitrazepam is a controlled substance available from Mylan. It is prescribed for severe insomnia and is sometimes used before surgery to induce a calm, relaxed state of mind for the patient.
  • In Sweden, flunitrazepam was previously available from Mylan, but has been removed from the market in January 2020. It is listed as a List II (Schedule II) under the Narcotics Control Act (1968).
  • In the United Kingdom, flunitrazepam is not licensed for medical use and is a controlled drug under Schedule 3 and Class C.
  • In the United States, the drug has not been approved by the Food and Drug Administration and is considered to be an illegal drug; as of 2016 it is Schedule IV. 21 U.S.C. § 841 and 21 U.S.C. § 952 provide for punishment for the importation and distribution of up to 20 years in prison and a fine; possession is punishable by three years and a fine. Travelers travelling into the United States are limited to a 30-day supply. The drug must be declared to US Customs upon arrival. If a valid prescription cannot be produced, the drug may be subject to Customs search and seizure, and the traveller may face criminal charges or deportation.

Names

Flunitrazepam is marketed under many brand names in the countries where it is legal. It also has many street names, including “roofie” and “ruffie”. It is also known as Circles, Forget Me Pill, La Rocha, Lunch Money Drug, Mexican Valium, Pingus, R2, and Roach 2.

On This Day … 22 October

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People (Births)

  • 1920 – Timothy Leary, American psychologist and author (d. 1996).

People (Deaths)

  • 1952 – Ernst Rüdin, Swiss psychiatrist, geneticist, and eugenicist (b. 1874).
  • 1979 – Mieko Kamiya, Japanese psychiatrist and author (b. 1914).

Timothy Leary

Timothy Francis Leary (22 October 1920 to 31 May 1996) was an American psychologist and writer known for his strong advocacy of psychedelic drugs. Evaluations of Leary are polarised, ranging from bold oracle to publicity hound. He was “a hero of American consciousness”, according to Allen Ginsberg, and Tom Robbins called him a “brave neuronaut.”

As a clinical psychologist at Harvard University, Leary worked on the Harvard Psilocybin Project from 1960 to 1962. He tested the therapeutic effects of lysergic acid diethylamide (LSD) and psilocybin, which were still legal in the United States at the time, in the Concord Prison Experiment and the Marsh Chapel Experiment. The scientific legitimacy and ethics of his research were questioned by other Harvard faculty because he took psychedelics along with research subjects and pressured students to join in. However, the claims that Leary pressured unwilling students are refuted by at least one of Leary’s students, Robert Thurman. Leary and his colleague, Richard Alpert (who later became known as Ram Dass), were fired from Harvard University in May 1963. Many people of the time only came to know of psychedelics after the Harvard scandal.

Leary believed that LSD showed potential for therapeutic use in psychiatry. He used LSD himself and developed a philosophy of mind expansion and personal truth through LSD. After leaving Harvard, he continued to publicly promote the use of psychedelic drugs and became a well-known figure of the counterculture of the 1960s. He popularized catchphrases that promoted his philosophy, such as “turn on, tune in, drop out”, “set and setting”, and “think for yourself and question authority”. He also wrote and spoke frequently about transhumanist concepts of space migration, intelligence increase, and life extension (SMI²LE). Leary developed the eight-circuit model of consciousness in his book Exo-Psychology (1977) and gave lectures, occasionally billing himself as a “performing philosopher.”

During the 1960s and 1970s, he was arrested 36 times worldwide. President Richard Nixon once described Leary as “the most dangerous man in America”.

Ernst Rudin

Ernst Rüdin (19 April 1874 to 22 October 1952) was a Swiss-born German psychiatrist, geneticist, eugenicist and Nazi. Rising to prominence under Emil Kraepelin and assuming his directorship at what is now called the Max Planck Institute of Psychiatry in Munich. While he has been credited as a pioneer of psychiatric inheritance studies, he also argued for, designed, justified and funded the mass sterilisation and clinical killing of adults and children.

Mieko Kamiya

Mieko Kamiya (神谷 美恵子, Kamiya Mieko, 12 January 1914 to 22 October 1979) was a Japanese psychiatrist who treated leprosy patients at Nagashima Aiseien Sanatorium.

She was known for translating books on philosophy. She worked as a medical doctor in the Department of Psychiatry at Tokyo University following World War II. She was said to have greatly helped the Ministry of Education and the General Headquarters, where the Supreme Commander of the Allied Powers stayed, in her role as an English-speaking secretary, and served as an adviser to Empress Michiko. She wrote many books as a highly educated, multi-lingual person; one of her books, titled On the Meaning of Life (Ikigai Ni Tsuite in Japanese), based on her experiences with leprosy patients, attracted many readers.

What is Emotional Dysregulation?

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Introduction

Emotional dysregulation is a term used in the mental health community that refers to emotional responses that are poorly modulated and do not lie within the accepted range of emotive response.

Refer to Emotional Self-Regulation.

Emotional dysregulation can be associated with an experience of early psychological trauma, brain injury, or chronic maltreatment (such as child abuse, child neglect, or institutional neglect/abuse), and associated disorders such as reactive attachment disorder. Emotional dysregulation may be present in people with psychiatric disorders such as attention deficit hyperactivity disorder, autism spectrum disorders, bipolar disorder, borderline personality disorder, complex post-traumatic stress disorder, and foetal alcohol spectrum disorders. In such cases as borderline personality disorder and complex post-traumatic stress disorder, hypersensitivity to emotional stimuli causes a slower return to a normal emotional state. This is manifested biologically by deficits in the frontal cortices of the brain.

Possible manifestations of emotional dysregulation include extreme tearfulness, angry outbursts or behavioural outbursts such as destroying or throwing objects, aggression towards self or others, and threats to kill oneself. Emotional dysregulation can lead to behavioural problems and can interfere with a person’s social interactions and relationships at home, in school, or at place of employment.

Etymology

The word “dysregulation” is a neologism created by combining the prefix “dys-” to “regulation”. According to Webster’s Dictionary, dys- has various roots and is of Greek origin. With Latin and Greek roots, it is akin to Old English tō-, te- “apart” and in Sanskrit dus- “bad, difficult.” It is frequently confused with the spelling “disregulation” with the prefix “dis” meaning “the opposite of” or “absence of”.

Child psychopathology

There are links between child emotional dysregulation and later psychopathology. For instance, ADHD symptoms are associated with problems with emotional regulation, motivation, and arousal. One study found a connection between emotional dysregulation at 5 and 10 months, and parent-reported problems with anger and distress at 18 months. Low levels of emotional regulation behaviours at 5 months were also related to non-compliant behaviours at 30 months. While links have been found between emotional dysregulation and child psychopathology, the mechanisms behind how early emotional dysregulation and later psychopathology are related are not yet clear.

Symptoms

Smoking, self-harm, eating disorders, and addiction have all been associated with emotional dysregulation. Somatoform disorders may be caused by a decreased ability to regulate and experience emotions or an inability to express emotions in a positive way. Individuals who have difficulty regulating emotions are at risk for eating disorders and substance abuse as they use food or substances as a way to regulate their emotions. Emotional dysregulation is also found in people who have an increased risk of developing a mental disorder, in particularly an affective disorder such as depression or bipolar disorder.

Early Childhood

Research has shown that failures in emotional regulation may be related to the display of acting out, externalizing disorders, or behaviour problems. When presented with challenging tasks, children who were found to have defects in emotional regulation (high-risk) spent less time attending to tasks and more time throwing tantrums or fretting than children without emotional regulation problems (low-risk). These high-risk children had difficulty with self-regulation and had difficulty complying with requests from caregivers and were more defiant. Emotional dysregulation has also been associated with childhood social withdrawal. Common signs of emotional dysregulation in early childhood include isolation, throwing things, screaming, lack of eye contact, refusing to speak, rocking, running away, crying, dissociating, high levels of anxiety, or inability to be flexible.

Internalising Behaviours

Emotional dysregulation in children can be associated with internalizing behaviours including:

  • Exhibiting emotions too intense for a situation.
  • Difficulty calming down when upset.
  • Difficulty decreasing negative emotions.
  • Being less able to calm themselves.
  • Difficulty understanding emotional experiences.
  • Becoming avoidant or aggressive when dealing with negative emotions.
  • Experiencing more negative emotions.

Externalising Behaviours

Emotional dysregulation in children can be associated with externalizing behaviours including:

  • Exhibiting more extreme emotions.
  • Difficulty identifying emotional cues.
  • Difficulty recognizing their own emotions.
  • Focusing on the negative.
  • Difficulty controlling their attention.
  • Being impulsive.
  • Difficulty decreasing their negative emotions.
  • Difficulty calming down when upset.

Protective Factors

Early experiences with caregivers can lead to differences in emotional regulation. The responsiveness of a caregiver to an infant’s signals can help an infant regulate their emotional systems. Caregiver interaction styles that overwhelm a child or that are unpredictable may undermine emotional regulation development. Effective strategies involve working with a child to support developing self-control such as modelling a desired behaviour rather than demanding it.

The richness of an environment that a child is exposed to helps the development of emotional regulation. An environment must provide appropriate levels of freedom and constraint. The environment must allow opportunities for a child to practice self-regulation. An environment with opportunities to practice social skills without over-stimulation or excessive frustration helps a child develop self-regulation skills.

Emotional Dysregulation and Substance Use

Several variables have been explored to explain the connection between emotional dysregulation and substance use in young adults, such as child maltreatment, cortisol levels, family environment, and symptoms of depression and anxiety. Vilhena-Churchill and Goldstein (2014) explored the association between childhood maltreatment and emotional dysregulation. More severe childhood maltreatment was found to be associated with an increase in difficulty regulating emotion, which in turn was associated with a greater likelihood of coping by using marijuana. Kliewer et al. (2016) performed a study on the relationship between negative family emotional climate, emotional dysregulation, blunted anticipatory cortisol, and substance use in adolescents. Increased negative family emotional climate was found to be associated with high levels of emotional dysregulation, which was then associated with increased substance use. Girls were seen to have blunted anticipatory cortisol levels, which was also associated with an increase in substance use. Childhood events and family climate with emotional dysregulation are both factors seemingly linked to substance use. Prosek, Giordano, Woehler, Price, and McCullough (2018) explored the relationship between mental health and emotional regulation in collegiate illicit substance users. Illicit drug users reported higher levels of depression and anxiety symptoms. Emotional dysregulation was more prominent in illicit drug users in the sense that they had less clarity and were less aware of their emotions when the emotions were occurring.

Treatment

While cognitive behavioural therapy is the most widely prescribed treatment for such psychiatric disorders, a commonly prescribed psychotherapeutic treatment for emotional dysregulation is dialectical behavioural therapy, a psychotherapy which promotes the use of mindfulness, a concept called dialectics, and emphasizes the importance of validation and maintaining healthy behavioural habits.

When diagnosed as being part of ADHD, norepinephrine and dopamine reuptake inhibitors such as methylphenidate (Ritalin) and atomoxetine are often used.

References

Kliewer, W., Riley, T., Zaharakis, N., Borre, A., Drazdowski, T.K. & Jäggi, L. (2016) Emotion Dysregulation, Anticipatory Cortisol, and Substance Use in Urban Adolescents. Personality and Individual Differences. 99, pp.200-205. doi:10.1016/j.paid.2016.05.011. PMC 5082236. PMID 27795602.

Prosek, E.A., Giordano, A.L., Woehler, E.S., Price, E. & McCullough, R. (2018) Differences in Emotion Dysregulation and Symptoms of Depression and Anxiety among Illicit Substance Users and Nonusers. Substance Use & Misuse. 53(11), pp.1915-1918. doi:10.1080/10826084.2018.1436563. PMID 29465278. S2CID 3411848.

Vilhena-Churchill, N. & Goldstein, A.L. (2014) Child Maltreatment and Marijuana Problems in Young Adults: Examining the Role of Motives and Emotion Dysregulation. Child Abuse & Neglect. 38(5), pp.962-972. doi:10.1016/j.chiabu.2013.10.009. PMID 24268374.

On This Day … 21 October

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People (Deaths)

  • 1980 – Hans Asperger, Austrian physician and psychologist (b. 1906).

Hans Asperger

Johann Friedrich Karl Asperger (18 February 1906 to 21 October 1980) was an Austrian physician.

Noted for his early studies on atypical neurology, specifically in children, he is the namesake of the autism spectrum disorder Asperger syndrome. He wrote over 300 publications on psychological disorders that posthumously acquired international renown in the 1980s. His diagnosis of autism, which he termed “autistic psychopathy”, has also garnished controversy. Further controversy arose during the late 2010s over allegations that Asperger referred children to a Nazi German clinic responsible for murdering disabled patients, although his knowledge and involvement remains unknown.

What is Depressive Personality Disorder?

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Introduction

Depressive personality disorder (also known as melancholic personality disorder) is a psychiatric diagnosis that denotes a personality disorder with depressive features.

Originally included in the American Psychiatric Association’s DSM-II, depressive personality disorder was removed from the DSM-III and DSM-III-R. Recently, it has been reconsidered for reinstatement as a diagnosis. Depressive personality disorder is currently described in Appendix B in the DSM-IV-TR as worthy of further study. Although no longer listed as a personality disorder, the diagnosis is included under the section “personality disorder not otherwise specified”.

While depressive personality disorder shares some similarities with mood disorders such as dysthymia, it also shares many similarities with personality disorders including avoidant personality disorder. Some researchers argue that depressive personality disorder is sufficiently distinct from these other conditions so as to warrant a separate diagnosis.

Characteristics

The DSM-IV defines depressive personality disorder as “a pervasive pattern of depressive cognitions and behaviors beginning by early adulthood and occurring in a variety of contexts.” Depressive personality disorder occurs before, during, and after major depressive episodes, making it a distinct diagnosis not included in the definition of either major depressive episodes or dysthymic disorder. Specifically, five or more of the following must be present most days for at least two years in order for a diagnosis of depressive personality disorder to be made:

  • Usual mood is dominated by dejection, gloominess, cheerlessness, joylessness and unhappiness.
  • Self-concept centres on beliefs of inadequacy, worthlessness and low self-esteem.
  • Is critical, blaming and derogatory towards the self.
  • Is brooding and given to worry.
  • Is negativistic, critical and judgmental toward others.
  • Is pessimistic.
  • Is prone to feeling guilty or remorseful.

People with depressive personality disorder have a generally gloomy outlook on life, themselves, the past and the future. They are plagued by issues developing and maintaining relationships. In addition, studies have found that people with depressive personality disorder are more likely to seek psychotherapy than people with Axis I depression spectra diagnoses.

Recent studies have concluded that people with depressive personality disorder are at a greater risk of developing dysthymic disorder than a comparable group of people without depressive personality disorder. These findings lead to the fact that depressive personality disorder is a potential precursor to dysthymia or other depression spectrum diagnoses. If included in the DSM-V, depressive personality disorder would be included as a warning sign for potential development of more severe depressive episodes.

DSM-5

Similarities to Dysthymic Disorder

Much of the controversy surrounding the potential inclusion of depressive personality disorder in the DSM-5 stems from its apparent similarities to dysthymic disorder, a diagnosis already included in the DSM-IV. Dysthymic disorder is characterised by a variety of depressive symptoms, such as hypersomnia or fatigue, low self-esteem, poor appetite, or difficulty making decisions, for over two years, with symptoms never numerous or severe enough to qualify as major depressive disorder. Patients with dysthymic disorder may experience social withdrawal, pessimism, and feelings of inadequacy at higher rates than other depression spectrum patients. Early-onset dysthymia is the diagnosis most closely related to depressive personality disorder.

The key difference between dysthymic disorder and depressive personality disorder is the focus of the symptoms used to diagnose. Dysthymic disorder is diagnosed by looking at the somatic senses, the more tangible senses. Depressive personality disorder is diagnosed by looking at the cognitive and intrapsychic symptoms. The symptoms of dysthymic disorder and depressive personality disorder may look similar at first glance, but the way these symptoms are considered distinguish the two diagnoses.

Comorbidity with other Disorders

Many researchers believe that depressive personality disorder is so highly comorbid with other depressive disorders, manic-depressive episodes and dysthymic disorder, that it is redundant to include it as a distinct diagnosis. Recent studies however, have found that dysthymic disorder and depressive personality disorder are not as comorbid as previously thought. It was found that almost two thirds of the test subjects with depressive personality disorder did not have dysthymic disorder, and 83% did not have early-onset dysthymia.

The comorbidity with Axis I depressive disorders is not as high as had been assumed. An experiment conducted by American psychologists showed that depressive personality disorder shows a high comorbidity rate with major depression experienced at some point in a lifetime and with any mood disorders experienced at any point in a lifetime. A high comorbidity rate with these disorders is expected of many diagnoses. As for the extremely high comorbidity rate with mood disorders, it has been found that essentially all mood disorders are comorbid with at least one other, especially when looking at a lifetime sample size.