Antipsychotic switching

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Risperdal Consta is a long-acting injectable antipsychotic, a type of antipsychotic that may be considered for antipsychotic switching if a patient is nonadherent to taking their antipsychotic medicine by mouth every day. Risperdal Consta injection syringe.jpg
Risperdal Consta is a long-acting injectable antipsychotic, a type of antipsychotic that may be considered for antipsychotic switching if a patient is nonadherent to taking their antipsychotic medicine by mouth every day.

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 theorized 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.

Contents

Rationale

Antipsychotics may be switched due to inadequate efficacy, drug intolerance, patient/guardian preference, drug regimen simplification, or for economic reasons. [1]

  1. Inadequate efficacy: 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. For example, this can refer to a patient who becomes acutely psychotic after being stable previously. 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. For example, long acting injectable (LAI) antipsychotics are often indicated in the setting of medication nonadherence. [1]
  2. Drug intolerance : Adverse effects can contribute to drug intolerance, potentially necessitating antipsychotic switching. 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. Certain drug interactions can cause adverse effects as well. [1]
  3. Patient/guardian preference: A patient or caregiver may prefer a different antipsychotic. 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. [1]
  4. Drug regimen simplification: 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. [1] For example, risperidone can be administered once daily. [4] A lack of adherence can lead to poor health outcomes, as well as unnecessary financial burden. [5]
  5. Economics : A patient or caregiver may request antipsychotic switching to reduce medication costs. [1] See below for a table of the direct costs of living with schizophrenia per patient across countries.
Cost of schizophrenia per patient by country
CountryAnnual direct costs (in US dollars)
Belgium 12,050 [6]
People's Republic of China 700 [7]
South Korea 2,600 [7]
Taiwan 2,115 to 2,144 [7]
United Kingdom 3,420 [6]
United States 15,464 [7]

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 behavior, violent behavior, or significant self-neglect or other symptoms. [1]

Strategies

There are multiple strategies available for switching antipsychotics. An abrupt switch involves abruptly switching from one antipsychotic to the other without any titration. [8] A cross-taper is accomplished by gradually discontinuing the pre-switch antipsychotic while simultaneously up-titrating the new antipsychotic. [1] 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. [1] Alternatively, in an ascending taper switch, the pre-switch antipsychotic can be abruptly discontinued. [8] Another alternative, known as the descending taper switch, involves slowly discontinuing the pre-switch antipsychotic while abruptly starting the new antipsychotic. [8] These switching strategies can be further subdivided by the inclusion or exclusion of a plateau period. [8]

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

Antipsychotic Switching Diagram.jpg

Due to differences in how individual antipsychotics work, even within each generation, the process of switching between antipsychotics has become more complex. [8]

Adverse effects

The three major adverse effects of antipsychotic switching are supersensitivity syndromes, withdrawal, and rebound syndromes. [8]

Supersensitivity syndromes

Antipsychotics work by antagonizing the dopamine receptor D2 (D2R) in the mesolimbic pathway of the brain. When the D2R is suppressed, the neurons may become sensitized 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 sensitized 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. [8]

Rebound syndromes

The second-generation antipsychotic olanzapine is thought to have a rebound-induced hyperthermia, which may be mediated by serotonin receptors. [8] Hyperthermia, or elevated core body temperature, is associated with neuroleptic malignant syndrome, a potentially lethal syndrome that commonly occurs due to excessive D2R antagonism. [9] [note 1]

In general, rebound D2R activity may induce rebound parkinsonism and rebound akathisia. [8]

Withdrawal

D2 receptor activity withdrawal may induce withdrawal dyskinesia. [8] 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. [8] Other symptoms of dopamine withdrawal include difficulty sleeping, anxiety, and restlessness. [11]

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. [12]

Notes

  1. As a point of contrast, hypothermia, or low core body temperature, has most frequently occurred in the presence of olanzapine, risperidone, or haloperidol. [10]

Related Research Articles

<span class="mw-page-title-main">Antipsychotic</span> Class of medications

Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay together with mood stabilizers in the treatment of bipolar disorder.

<span class="mw-page-title-main">Haloperidol</span> Typical antipsychotic medication

Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks by people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.

<span class="mw-page-title-main">Atypical antipsychotic</span> Class of pharmaceutical drugs

The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, irritability in autism, and as an adjunct in major depressive disorder.

<span class="mw-page-title-main">Risperidone</span> Antipsychotic medication

Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection. The injectable versions are long-acting and last for 2–4 weeks.

<span class="mw-page-title-main">Quetiapine</span> Atypical antipsychotic medication

Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, borderline personality disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its sedating effect, the benefits of such use do not appear to generally outweigh the side effects. It is taken orally.

<span class="mw-page-title-main">Ziprasidone</span> Antipsychotic medication

Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitation in people with schizophrenia.

<span class="mw-page-title-main">Olanzapine</span> Atypical antipsychotic medication

Olanzapine is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.

<span class="mw-page-title-main">Perphenazine</span> Antipsychotic medication

Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. Originally marketed in the United States as Trilafon, it has been in clinical use for decades.

<span class="mw-page-title-main">Aripiprazole</span> Atypical antipsychotic

Aripiprazole, sold under the brand names Abilify and Aristada, among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia, obsessive compulsive disorder (OCD), and bipolar disorder; other uses include as an add-on treatment in major depressive disorder, tic disorders, and irritability associated with autism. Aripiprazole is taken by mouth or via injection into a muscle. A Cochrane review found low-quality evidence of effectiveness in treating schizophrenia.

<span class="mw-page-title-main">Sertindole</span> Antipsychotic medication

Sertindole, sold under the brand name Serdolect among others, is an antipsychotic medication. Sertindole was developed by the Danish pharmaceutical company Lundbeck and marketed under license by Abbott Labs. Like other atypical antipsychotics, it has activity at dopamine and serotonin receptors in the brain. It is used in the treatment of schizophrenia. It is classified chemically as a phenylindole derivative.

<span class="mw-page-title-main">Prochlorperazine</span> Medication for nausea, psychosis, and anxiety

Prochlorperazine, formerly sold under the brand name Compazine among others, is a medication used to treat nausea, migraines, schizophrenia, psychosis and anxiety. It is a less preferred medication for anxiety. It may be taken by mouth, rectally, injection into a vein, or injection into a muscle.

The rebound effect, or rebound phenomenon, is the emergence or re-emergence of symptoms that were either absent or controlled while taking a medication, but appear when that same medication is discontinued, or reduced in dosage. In the case of re-emergence, the severity of the symptoms is often worse than pretreatment levels.

<span class="mw-page-title-main">Amisulpride</span> Atypical antipsychotic and antiemetic medication

Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. At very low doses it is also used to treat dysthymia.

<span class="mw-page-title-main">Paliperidone</span> Antipsychotic medication

Paliperidone, sold under the trade name Invega among others, is an atypical antipsychotic. It is mainly used to treat schizophrenia and schizoaffective disorder.

<span class="mw-page-title-main">Asenapine</span> Medication to treat schizophrenia

Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder as well as the medium to long-term management of bipolar disorder.

<span class="mw-page-title-main">Iloperidone</span> Chemical compound

Iloperidone, commonly known as Fanapt and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia.

<span class="mw-page-title-main">Perospirone</span> Chemical compound that acts as an atypical antipsychotic

Perospirone (Lullan) is an atypical antipsychotic of the azapirone family. It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania.

<span class="mw-page-title-main">Pimavanserin</span> Chemical compound

Pimavanserin, sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis and is also being studied for the treatment of Alzheimer’s disease psychosis, schizophrenia, agitation, and major depressive disorder. Unlike other antipsychotics, pimavanserin is not a dopamine receptor antagonist.

<span class="mw-page-title-main">Aripiprazole lauroxil</span> Chemical compound

Aripiprazole lauroxil, sold under the brand name Aristada, is a long-acting injectable atypical antipsychotic that was developed by Alkermes. It is an N-acyloxymethyl prodrug of aripiprazole that is administered via intramuscular injection once every four to eight weeks for the treatment of schizophrenia. Aripiprazole lauroxil was approved by the U.S. Food and Drug Administration (FDA) on 5 October 2015.

Dopamine supersensitivity psychosis is a hypothesis that attempts to explain the phenomenon in which psychosis occurs despite treatment with escalating doses of antipsychotics. Dopamine supersensitivity may be caused by the dopamine receptor D2 antagonizing effect of antipsychotics, causing a compensatory increase in D2 receptors within the brain that sensitizes neurons to endogenous release of the neurotransmitter dopamine. Because psychosis is thought to be mediated—at least in part—by the activity of dopamine at D2 receptors, the activity of dopamine in the presence of supersensitivity may paradoxically give rise to worsening psychotic symptoms despite antipsychotic treatment at a given dose. This phenomenon may co-occur with tardive dyskinesia, a rare movement disorder that may also be due to dopamine supersensitivity.

References

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