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What is Antipsychotic Switching?

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Introduction

Antipsychotic switching refers to the process of switching out one antipsychotic for another antipsychotic.

There are multiple indications for switching antipsychotics, including inadequate efficacy and drug intolerance. There are several strategies that have been theorised for antipsychotic switching, based upon the timing of discontinuation and tapering of the original antipsychotic and the timing of initiation and titration of the new antipsychotic. Major adverse effects from antipsychotic switching may include supersensitivity syndromes, withdrawal, and rebound syndromes.

Rationale

Antipsychotics may be switched due to inadequate efficacy, drug intolerance, patient/guardian preference, drug regimen simplification, or for economic reasons.

RationaleOutline
Inadequate Efficacy1. An inadequate treatment response to an antipsychotic, assuming that the lack of efficacy is due to an otherwise adequately dosed regimen for an appropriate duration, can result from failure to achieve therapeutic goals in any major treatment domain.
2. For example, this can refer to a patient who becomes acutely psychotic after being stable previously.
3. Other failures include persistent symptoms of schizophrenia, either positive or negative, problems with mood (including suicidality), or problems with cognition. Inadequate efficacy may be due to nonadherence to therapy, which can influence treatment decisions.
4. For example, long acting injectable (LAI) antipsychotics are often indicated in the setting of medication nonadherence.
Drug Intolerance1. Adverse effects can contribute to drug intolerance, potentially necessitating antipsychotic switching.
2. Adverse effects that threaten serious harm, aggravate other medical conditions, or make a person want to stop taking their medications are all examples of drug intolerance.
3. Certain drug interactions can cause adverse effects as well.
Patient/Guardian Preference1. A patient or caregiver may prefer a different antipsychotic.
2. This may be due to misinformation regarding the antipsychotic, including its side effects, a lack of insight into the importance of the medication and the severity of the disease, or overestimating the therapeutic effect.
Drug Regimen Simplification1. Adherence to medication therapy is inversely related to the frequency of dosing.
2. The antipsychotic quetiapine is typically dosed two to three times daily for the management of schizophrenia.
3. A simpler regimen would be a once daily administered antipsychotic.
4. For example, risperidone can be administered once daily.
5. A lack of adherence can lead to poor health outcomes, as well as unnecessary financial burden.
Economics1. A patient or caregiver may request antipsychotic switching to reduce medication costs.
2. The following is an estimate of the direct costs of living with schizophrenia per patient across select countries (annual direct costs in US$):
a. Belgium: 12,050.
b. People’s Republic of China: 700.
c. South Korea: 2,600.
d. Taiwan: 2,115.
e. UK: 3,420.
f. US: 15,464.

Contraindications

In general, contraindications to antipsychotic switching are cases in which the risk of switching outweighs the potential benefit. Contraindications to antipsychotic switching include effective treatment of an acute psychotic episode, patients stable on a LAI antipsychotic with a history of poor adherence, and stable patients with a history of self-injurious behaviour, violent behaviour, or significant self-neglect or other symptoms.

Strategies

There are multiple strategies available for switching antipsychotics. An abrupt switch involves abruptly switching from one antipsychotic to the other without any titration. A cross-taper is accomplished by gradually discontinuing the pre-switch antipsychotic while simultaneously up-titrating the new antipsychotic. An overlap and discontinuation switch involves maintaining the pre-switch antipsychotic until the new antipsychotic is gradually titrated up, then gradually titrating down on the pre-switch antipsychotic. Alternatively, in an ascending taper switch, the pre-switch antipsychotic can be abruptly discontinued. Another alternative, known as the descending taper switch, involves slowly discontinuing the pre-switch antipsychotic while abruptly starting the new antipsychotic. These switching strategies can be further subdivided by the inclusion or exclusion of a plateau period.

See the figure below for a graphic visualisation of the five main antipsychotic switching strategies discussed above.

Antipsychotic Switching Diagram.

Due to differences in how individual antipsychotics work, even within each generation, the process of switching between antipsychotics has become more complex.

Adverse Effects

The three major adverse effects of antipsychotic switching are supersensitivity syndromes, withdrawal, and rebound syndromes.

Supersensitivity Syndromes

Antipsychotics work by antagonising the dopamine receptor D2 (D2R) in the mesolimbic pathway of the brain. When the D2R is suppressed, the neurons may become sensitised to the effect of an endogenous ligand (i.e. dopamine) by up-regulating the production of postsynaptic D2Rs. If the D2 receptors are not subsequently suppressed at previous levels after an abrupt discontinuation of an antipsychotic (e.g. after switching to weak D2R antagonists quetiapine or clozapine), a rebound/supersensitivity psychosis may occur due to the overwhelming effect of endogenous dopamine on sensitised neurons. Supersensitivity psychosis, also called rapid-onset psychosis, must be distinguished from a relapse or exacerbation of the underlying disease (e.g. schizophrenia). Dopamine supersensitivity psychosis generally occurs around 6 weeks after an oral antipsychotic is discontinued, or 3 months after a LAI antipsychotic is discontinued. In addition, supersensitivity psychosis is generally easier to reverse by reintroducing D2R antagonism (i.e. restarting the discontinued drug), whereas a relapsed schizophrenia is more difficult to control.

Rebound Syndromes

The second-generation antipsychotic olanzapine is thought to have a rebound-induced hyperthermia, which may be mediated by serotonin receptors. Hyperthermia, or elevated core body temperature, is associated with neuroleptic malignant syndrome, a potentially lethal syndrome that commonly occurs due to excessive D2R antagonism (As a point of contrast, hypothermia, or low core body temperature, has most frequently occurred in the presence of olanzapine, risperidone, or haloperidol).

In general, rebound D2R activity may induce rebound parkinsonism and rebound akathisia.

Withdrawal

D2 receptor activity withdrawal may induce withdrawal dyskinesia. This late-onset, hypersensitivity-type dyskinesia is in contrast to the early-onset dyskinesia that can occur due to an over-compensatory dopamine release associated with abrupt dopamine antagonist withdrawal. Other symptoms of dopamine withdrawal include difficulty sleeping, anxiety, and restlessness.

Alternatives

An alternative to antipsychotic switching, in the setting of a person that is not responding to the initial dose of an antipsychotic, is to increase the dose of antipsychotic prescribed. A 2018 Cochrane review compared the evidence between the two strategies, but the authors were unable to draw any conclusions about whether either method was preferable due to limited evidence.

On This Day … 01 February

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People (Births)

  • 1844 – G. Stanley Hall, American psychologist and academic (d. 1924).

G. Stanley Hall

Granville Stanley Hall (01 February 1846 to 24 April 1924) was a pioneering American psychologist and educator.

His interests focused on human life span development and evolutionary theory. Hall was the first president of the American Psychological Association and the first president of Clark University. A Review of General Psychology survey, published in 2002, ranked Hall as the 72nd most cited psychologist of the 20th century, in a tie with Lewis Terman.

What is Transference?

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Introduction

Transference (German: Übertragung) is a phenomenon within psychotherapy in which the feelings a person had about their parents, as one example, are unconsciously redirected or transferred to the present situation.

It usually concerns feelings from a primary relationship during childhood. At times, this transference can be considered inappropriate. Transference was first described by Sigmund Freud, the founder of psychoanalysis, who considered it an important part of psychoanalytic treatment.

Occurrence

It is common for people to transfer feelings about their parents to their partners or children (that is, cross-generational entanglements). Another example of transference would be a person mistrusting somebody who resembles an ex-spouse in manners, voice, or external appearance, or being overly compliant to someone who resembles a childhood friend.

In The Psychology of the Transference, Carl Jung states that within the transference dyad both participants typically experience a variety of opposites, that in love and in psychological growth, the key to success is the ability to endure the tension of the opposites without abandoning the process, and that this tension allows one to grow and to transform.

Only in a personally or socially harmful context can transference be described as a pathological issue. A modern, social-cognitive perspective on transference explains how it can occur in everyday life. When people meet a new person who reminds them of someone else, they unconsciously infer that the new person has traits similar to the person previously known. This perspective has generated a wealth of research that illuminated how people tend to repeat relationship patterns from the past in the present.

High-profile serial killers often transfer unresolved rage toward previous love or hate-objects onto “surrogates”, or individuals resembling or otherwise calling to mind the original object of that hate. It is believed in the instance of Ted Bundy, he repeatedly killed brunette women who reminded him of a previous girlfriend with whom he had become infatuated, but who had ended the relationship, leaving Bundy rejected and pathologically rageful (Bundy, however, denied this as a motivating factor in his crimes). This notwithstanding, Bundy’s behaviour could be considered pathological insofar as he may have had narcissistic or antisocial personality disorder. If so, normal transference mechanisms cannot be held causative of his homicidal behaviour.

Sigmund Freud held that transference plays a large role in male homosexuality. In The Ego and the Id, he claimed that eroticism between males can be an outcome of a “[psychically] non-economic” hostility, which is unconsciously subverted into love and sexual attraction.

Transference and Counter-Transference during Psychotherapy

In a therapy context, transference refers to redirection of a patient’s feelings for a significant person to the therapist. Transference is often manifested as an erotic attraction towards a therapist, but can be seen in many other forms such as rage, hatred, mistrust, parentification, extreme dependence, or even placing the therapist in a god-like or guru status. When Freud initially encountered transference in his therapy with patients, he thought he was encountering patient resistance, as he recognised the phenomenon when a patient refused to participate in a session of free association. But what he learned was that the analysis of the transference was actually the work that needed to be done: “the transference, which, whether affectionate or hostile, seemed in every case to constitute the greatest threat to the treatment, becomes its best tool”. The focus in psychodynamic psychotherapy is, in large part, the therapist and patient recognising the transference relationship and exploring the relationship’s meaning. Since the transference between patient and therapist happens on an unconscious level, psychodynamic therapists who are largely concerned with a patient’s unconscious material use the transference to reveal unresolved conflicts patients have with childhood figures.

Countertransference is defined as redirection of a therapist’s feelings toward a patient, or more generally, as a therapist’s emotional entanglement with a patient. A therapist’s attunement to their own countertransference is nearly as critical as understanding the transference. Not only does this help therapists regulate their emotions in the therapeutic relationship, but it also gives therapists valuable insight into what patients are attempting to elicit in them. For example, a therapist who is sexually attracted to a patient must understand the countertransference aspect (if any) of the attraction, and look at how the patient might be eliciting this attraction. Once any countertransference aspect has been identified, the therapist can ask the patient what his or her feelings are toward the therapist, and can explore how those feelings relate to unconscious motivations, desires, or fears.

Another contrasting perspective on transference and countertransference is offered in classical Adlerian psychotherapy. Rather than using the patient’s transference strategically in therapy, the positive or negative transference is diplomatically pointed out and explained as an obstacle to cooperation and improvement. For the therapist, any signs of countertransference would suggest that his or her own personal training analysis needs to be continued to overcome these tendencies. Andrea Celenza noted in 2010 that “the use of the analyst’s countertransference remains a point of controversy”.

What is a Therapeutic Alliance?

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Introduction

A therapeutic alliance, or working alliance, is a partnership between a patient and their therapist that allows them to achieve goals through agreed-upon tasks.

The concept of therapeutic alliance dates back to Sigmund Freud. Over the course of its evolution, the meaning of the therapeutic alliance has shifted both in form and implication. What started as an analytic construct has become, over the years, a transtheoretical formulation, an integrative variable, and a common factor.

Alliance as Analytic

In its analytic permutation, Freud suggested the importance of allowing for the patient to be a “collaborator” in the therapeutic process. In his writings on transference, Freud thought of the patient’s feelings towards the therapist as resembling the non-conflicted, trusting elements of early relationships with the patient’s parents, and that this could serve as the basis for collaboration in this way.

In later years, ego psychologists popularised a construct that they would relate to the reality-oriented adaptation of the ego to the environment. For certain ego psychologists, the construct refocused psychoanalytic thought away from a perceived overemphasis on transference and allowed space for greater technical flexibility across different psychotherapeutic modalities. It also called into question the idea of therapist as a tabula rasa, or blank screen, and turned away from the idealised therapist stance of abstinence and neutrality. Instead, it brought attention to the real, felt dimension of the therapeutic relationship, and made an argument for the therapist as being supportive and the patient as identifying with the therapist.

Alliance as Integrative

Edward Bordin reformulated the therapeutic alliance more broadly, namely beyond the scope of the psychodynamic perspective, as transtheoretical. He operationalised the construct into three interdependent parts:

  • The affective bond between the patient and therapist;
  • Their agreement on goals; and
  • Their agreement on tasks.

This conceptualisation preserved the earlier focus on the affective aspects of the alliance (i.e. bond), while also incorporating more cognitive dimensions as well (i.e. tasks and goals). Bordin’s work led to a desire among researchers to further develop ways to measure the alliance based on his initial operationalisation. Around this time there was a surge of interest in psychotherapy integration and psychotherapy research on the alliance.

Alliance as Intersubjective

Jeremy Safran and J. Christopher Muran, along with their colleagues Catherine F. Eubanks and Lisa Wallner Samstag, advanced a further reformulation of the alliance. They agreed with Bordin that at an explicit level, patient and therapist collaborate on specific tasks. However, on an implicit level, they are also negotiating specific desires derived from underlying needs.

In this regard, the authors invoked the motivational needs for agency (self-definition) and communion (relatedness), and the existential need for mutual recognition (to see another’s subjectivity and to have another see one’s own as the culmination of knowing one exists), to advance an intersubjective consideration.

The authors suggested ruptures invariably occur as result of the inherent tensions in the negotiation of these dialectical needs. They distinguished between withdrawal and confrontation rupture markers, interpersonal communications or behaviour by patient or therapist.

  • The former includes movements away from self or other: that is, movements towards isolation or appeasement, pursuits of communion at the expense of agency.
  • The latter includes movements against the other: that is, movements towards control or aggression, pursuits of agency at the expense of communion. They defined the repair of these ruptures as a critical change process.

Alliance in Psychotherapy Research

Beginning in the 1970s, the alliance construct became a primary focus of psychotherapy research. This can be attributed largely to Bordin’s reformulation, which led to the development of Working Alliance Inventory (WAI) and Lester Luborsky’s Penn Helping Alliance Questionnaire (HAq). The Vanderbilt Psychotherapy Process Scales and the California Psychotherapy Alliance Scales (CALPAS) were other noteworthy measures.

Christoph Flückiger, AC Del Re, Bruce Wampold, and Adam Horvath conducted a meta-analysis on the alliance in psychotherapy. The researchers synthesized 295 independent studies of over 30,000 patients published 1978-2017. Results confirmed a moderate relationship between alliance and psychotherapy outcome.

In addition, Eubanks, Muran, and Safran conducted two meta-analyses on rupture repair in the alliance. The first indicated a moderate relationship between rupture repair and outcome. The second examined the effect of an alliance-focused training on rupture repair. Results suggested some support for the effect of such training.

On This Day .. 28 January

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People (Deaths)

  • 1971 – Donald Winnicott, English paediatrician and psychoanalyst (b. 1896).

David Winnicott

Donald Woods Winnicott FRCP (07 April 1896 to 25 January 1971) was an English paediatrician and psychoanalyst who was especially influential in the field of object relations theory and developmental psychology. He was a leading member of the British Independent Group of the British Psychoanalytical Society, President of the British Psychoanalytical Society twice (1956-1959 and 1965-1968), and a close associate of Marion Milner.

Winnicott is best known for his ideas on the true self and false self, the “good enough” parent, and borrowed from his second wife, Clare Winnicott, arguably his chief professional collaborator, the notion of the transitional object. He wrote several books, including Playing and Reality, and over 200 papers.

On This Day … 27 January

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People (Births)

  • 1904 – James J. Gibson, American psychologist and academic (d. 1979).

James J. Gibson

James Jerome Gibson (27 January 1904 to 11 December 1979), was an American psychologist and one of the most important contributors to the field of visual perception.

Gibson challenged the idea that the nervous system actively constructs conscious visual perception, and instead promoted ecological psychology, in which the mind directly perceives environmental stimuli without additional cognitive construction or processing.

A Review of General Psychology survey, published in 2002, ranked him as the 88th most cited psychologist of the 20th century, tied with John Garcia, David Rumelhart, Louis Leon Thurstone, Margaret Floy Washburn, and Robert S. Woodworth.

What is Self-Defeating Personality Disorder?

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Introduction

Self-defeating personality disorder (also known as masochistic personality disorder) was a proposed personality disorder.

It was discussed in an appendix of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) in 1987, but was never formally admitted into the manual. As an alternative, the diagnosis personality disorder not otherwise specified remains in use in the DSM-5. A classification proposed for future versions is the personality disorder-trait specified (PD-TS). Some researchers and theorists continue to use the DSM-III-R criteria. The official diagnostic code number was 301.90 (personality disorder NOS).

Refer to Self-Handicapping.

Diagnosis

Definition Proposed in DSM III-R for Further Review

Self-defeating personality disorder is:

  • A) A pervasive pattern of self-defeating behaviour, beginning by early adulthood and present in a variety of contexts. The person may often avoid or undermine pleasurable experiences, be drawn to situations or relationships in which they will suffer, and prevent others from helping them, as indicated by at least five of the following:
    1. Chooses people and situations that lead to disappointment, failure, or mistreatment even when better options are clearly available.
    2. Rejects or makes ineffective the attempts of others to help them.
    3. Following positive personal events (e.g. new achievement), responds with depression, guilt, or a behaviour that produces pain (e.g. an accident).
    4. Incites angry or rejecting responses from others and then feels hurt, defeated, or humiliated (e.g. makes fun of spouse in public, provoking an angry retort, then feels devastated).
    5. Rejects opportunities for pleasure, or is reluctant to acknowledge enjoying themselves (despite having adequate social skills and the capacity for pleasure).
    6. Fails to accomplish tasks crucial to their personal objectives despite having demonstrated ability to do so (e.g., helps fellow students write papers, but is unable to write their own).
    7. Is uninterested in or rejects people who consistently treat them well.
    8. Engages in excessive self-sacrifice that is unsolicited by the intended recipients of the sacrifice.
    9. The person may often avoid or undermine pleasurable experiences […]
  • B) The behaviors in A do not occur exclusively in response to, or in anticipation of, being physically, sexually, or psychologically abused.
  • C) The behaviors in A do not occur only when the person is depressed.

Exclusion from DSM-IV

Historically, masochism has been associated with feminine submissiveness. This disorder became politically controversial when associated with domestic violence which was considered to be mostly caused by males. However a number of studies suggest that the disorder is common. In spite of its exclusion from DSM-IV in 1994, it continues to enjoy widespread currency amongst clinicians as a construct that explains a great many facets of human behaviour.

Sexual masochism that “causes clinically significant distress or impairment in social, occupational, or other important areas of functioning” is still in DSM-IV.

What is an Atypical Antidepressant?

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Introduction

An atypical antidepressant is any antidepressant medication that acts in a manner that is different from that of most other antidepressants.

Refer to Second-Generation Antidepressant, Tricyclic Antidepressant, and Tetracyclic Antidepressant.

Background

Atypical antidepressants include agomelatine, bupropion, mianserin, mirtazapine, nefazodone, opipramol, tianeptine, and trazodone. The agents vilazodone and vortioxetine are partly atypical. Typical antidepressants include the SSRIs, SNRIs, TCAs, and MAOIs, which act mainly by increasing the levels of the monoamine neurotransmitters serotonin and/or norepinephrine. Among TCAs, trimipramine is an atypical agent in that it appears not to do this. In August 2020, Esketamine (JNJ-54135419) was approved by the US Food and Drug Administration (FDA) for the treatment for treatment-resistant depression with the added indication for the short-term treatment of suicidal thoughts.

Buprenorphine/Samidorphan (ALKS-5461) is an antidepressant with a novel mechanism of action which is under development and is considered an atypical antidepressant. They act faster than available antidepressants.

What is a Second-Generation Antidepressant?

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Introduction

The second-generation antidepressants are a class of antidepressants characterised primarily by the era of their introduction, approximately coinciding with the 1970s and 1980s, rather than by their chemical structure or by their pharmacological effect. As a consequence, there is some controversy over which treatments actually belong in this class.

Refer to Atypical Antidepressant, Tricyclic Antidepressant, and Tetracyclic Antidepressant.

The term “third generation antidepressant” is sometimes used to refer to newer antidepressants, from the 1990s and 2000s, often selective serotonin reuptake inhibitors (SSRIs) such as; fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft), as well as some non-SSRI antidepressants such as mirtazapine, nefazodone, venlafaxine, duloxetine and reboxetine. However, this usage is not universal.

Examples

This list is not exhaustive, and different sources vary upon which items should be considered second-generation.

  • Amineptine.
  • Amoxapine.
  • Bupropion.
  • Iprindole.
  • Maprotiline.
  • Medifoxamine.
  • Mianserin.
  • Nomifensine.
  • Tianeptine.
  • Trazodone.
  • Venlafaxine.
  • Viloxazine.

On This Day … 25 January

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People (Births)

  • 1923 – Shirley Ardell Mason, American psychiatric patient (d. 1998).

Shirley Ardell Mason

Shirley Ardell Mason (25 January 1923 to 26 February 1998) was an American art teacher who was reputed to have dissociative identity disorder (previously known as multiple personality disorder).

Her life was purportedly described, with adaptations to protect her anonymity, in 1973 in the book Sybil, subtitled The True Story of a Woman Possessed by 16 Separate Personalities. Two films of the same name were made, one released in 1976 and the other in 2007. Both the book and the films used the name Sybil Isabel Dorsett to protect Mason’s identity, though the 2007 remake stated Mason’s name at its conclusion.

Mason’s diagnosis and treatment under Cornelia B. Wilbur have been criticised, with allegations that Wilbur manipulated or possibly misdiagnosed Mason.