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Pronunciation | /kwɪˈtaɪ.əpiːn/ kwi-TY-ə-peen |
Trade names | Seroquel, Seroquel Xr, others |
AHFS/Drugs.com | Monograph |
MedlinePlus | a698019 |
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Routes of administration | By mouth |
Drug class | Atypical antipsychotic |
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Pharmacokinetic data | |
Bioavailability | 100% [6] |
Protein binding | 83% [7] |
Metabolism | Liver via CYP3A4-catalysed sulfoxidation to its active metabolite norquetiapine (N-desalkylquetiapine) [8] |
Elimination half-life | 7 hours (parent compound); 9–12 hours (active metabolite, norquetiapine) [7] [9] |
Excretion | Kidney (73%), feces (20%) [6] [7] [9] [10] |
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ECHA InfoCard | 100.131.193 |
Chemical and physical data | |
Formula | C21H25N3O2S |
Molar mass | 383.51 g·mol−1 |
3D model (JSmol) | |
Solubility in water | 3.29 mg/mL (20 °C) |
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Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. [11] [12] Despite being widely used as a sleep aid due to its tranquillizing effects, the benefits of such use may not outweigh the risk of undesirable side effects. [13] It is taken orally. [11]
Common side effects include sedation, fatigue, weight gain, constipation, and dry mouth. [11] Other side effects include low blood pressure with standing, seizures, a prolonged erection, high blood sugar, tardive dyskinesia, and neuroleptic malignant syndrome. [11] In older people with dementia, its use increases the risk of death. [11] Use in the third trimester of pregnancy may result in a movement disorder in the baby for some time after birth. [11] Quetiapine is believed to work by blocking a number of receptors, including those for serotonin and dopamine. [11]
Quetiapine was developed in 1985 and was approved for medical use in the United States in 1997. [4] [11] [14] It is available as a generic medication. [15] In 2022, it was the 82nd most commonly prescribed medication in the United States, with more than 8 million prescriptions. [16] [17] It is on the World Health Organization's List of Essential Medicines. [18]
Quetiapine is primarily used to treat schizophrenia or bipolar disorder. [19] Quetiapine targets both positive and negative symptoms of schizophrenia. [20]
A 2013 Cochrane review compared quetiapine to typical antipsychotics:
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Quetiapine may not differ from typical antipsychotics in the treatment of positive symptoms, general psychopathology, and negative symptoms. However, it causes fewer adverse effects in terms of abnormal ECG, extrapyramidal effects, abnormal prolactin levels and weight gain. [21] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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In a 2013 comparison of 15 antipsychotics in effectiveness in treating schizophrenia, quetiapine demonstrated standard effectiveness. It was 13–16% more effective than ziprasidone, chlorpromazine, and asenapine and approximately as effective as haloperidol and aripiprazole. [22]
There is tentative evidence of the benefit of quetiapine versus placebo in schizophrenia; however, definitive conclusions are not possible due to the high rate of attrition in trials (greater than 50%) and the lack of data on economic outcomes, social functioning, or quality of life. [23]
It is debatable whether, as a class, typical or atypical antipsychotics are more effective. [24] Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages. [25] While quetiapine has lower rates of extrapyramidal side effects, there is greater sleepiness and rates of dry mouth. [23]
A Cochrane review comparing quetiapine to other atypical antipsychotic agents tentatively concluded that it may be less efficacious than olanzapine and risperidone; produce fewer movement related side effects than paliperidone, aripiprazole, ziprasidone, risperidone and olanzapine; and produce weight gain similar to risperidone, clozapine and aripiprazole. They concluded that it produces suicide attempt, suicide; death; QTc prolongation, low blood pressure; tachycardia; sedation; gynaecomastia; galactorrhoea, menstrual irregularity and white blood cell count at a rate similar to first generation antipsychotics. [26]
In those with bipolar disorder, quetiapine is used to treat depressive episodes; acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium; valproate or lamotrigine); acute mixed episodes; and maintenance treatment of bipolar I disorder (as adjunct therapy to lithium or divalproex).
Quetiapine is effective when used by itself [12] and when used along with other medications in major depressive disorder (MDD). [12] [27] However, sedation is often an undesirable side effect. [12]
In the United States, [9] the United Kingdom [28] and Australia (while not subsidised by the Australian Pharmaceutical Benefits Scheme for treatment of MDD), quetiapine is licensed for use as an add-on treatment in MDD. [29]
Quetiapine does not decrease agitation among people with Alzheimer's disease. Quetiapine worsens intellectual functioning in the elderly with dementia and therefore is not recommended. [30]
The use of low doses of quetiapine for insomnia, while common, is not recommended; there is little evidence of benefit and concerns regarding adverse effects. [31] [32] [33] [34] [35] [36] A 2022 network meta-analysis of 154 double-blind, randomized controlled trials of drug therapies vs. placebo for insomnia in adults found that quetiapine did not demonstrate any short-term benefits in sleep quality. Quetiapine, specifically, had an effect size (standardized mean difference) against placebo for treatment of insomnia of 0.05 (95% CI –1.21 to 1.11) at 4 weeks of treatment, with the certainty of evidence rated as very low. [37] Doses of quetiapine used for insomnia have ranged from 12.5 to 800 mg, with low doses of 25 to 200 mg being the most typical. [38] [31] [32] Regardless of the dose used, some of the more serious adverse effects may still possibly occur at the lower dosing ranges, such as dyslipidemia and neutropenia. [39] [40] These safety concerns at low doses are corroborated by Danish observational studies that showed use of specifically low-dose quetiapine (prescriptions filled for tablet strengths >50 mg were excluded) was associated with an increased risk of major cardiovascular events as compared to use of Z-drugs, with most of the risk being driven by cardiovascular death. [41] Laboratory data from an unpublished analysis of the same cohort also support the lack of dose-dependency of metabolic side effects, as new use of low-dose quetiapine was associated with a risk of increased fasting triglycerides at 1-year follow-up. [42]
It is sometimes used off-label, often as an augmentation agent, to treat conditions such as Tourette syndrome, [43] musical hallucinations [44] and anxiety disorders. [45]
Quetiapine and clozapine are the most widely used medications for the treatment of Parkinson's disease psychosis due to their relatively low extrapyramidal side-effect liability. [46] Owing to the risks associated with clozapine (e.g. agranulocytosis, diabetes mellitus, etc.), clinicians often attempt treatment with quetiapine first, although the evidence to support quetiapine's use for this indication is significantly weaker than that of clozapine. [47] [48]
Sources for incidence lists: [6] [9] [28] [29] [48] [49]
Both typical and atypical antipsychotics can cause tardive dyskinesia. [50] According to one study, rates are lower with the atypicals at 3.9% as opposed to the typicals at 5.5%. [50] Although quetiapine and clozapine are atypical antipsychotics, switching to these atypicals is an option to minimize symptoms of tardive dyskinesia caused by other atypicals. [51]
Weight gain can be a problem for some, with quetiapine causing more weight gain than fluphenazine, haloperidol, loxapine, molindone, olanzapine, pimozide, risperidone, thioridazine, thiothixene, trifluoperazine, and ziprasidone, but less than chlorpromazine, clozapine, perphenazine, and sertindole. [52]
As with some other anti-psychotics, quetiapine may lower the seizure threshold, [53] and should be taken with caution in combination with drugs such as bupropion.
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. [54] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. [55] Other symptoms may include restlessness, increased sweating, and trouble sleeping. [55] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains. [55] Symptoms generally resolve after a short period of time. [55]
There is tentative evidence that discontinuation of antipsychotics can result in psychosis. [56] It may also result in reoccurrence of the condition that is being treated. [57] Rarely tardive dyskinesia can occur when the medication is stopped. [55]
Placental exposure is least for quetiapine compared to other atypical antipsychotics. [48] The evidence is insufficient to rule out any risk to the foetus but available data suggests it is unlikely to result in any major foetal malformations. [7] [10] [49] It is secreted in breast milk and hence quetiapine-treated mothers are advised not to breastfeed. [7] [10] [49]
In contrast to most other antipsychotic drugs, which tend to be somewhat aversive and often show problems with patient compliance with prescribed medication regimes, quetiapine is sometimes associated with drug misuse and abuse potential, for its hypnotic and sedative effects. It has a limited potential for misuse, usually only in individuals with a history of polysubstance abuse and/or mental illness, and especially in those incarcerated in prisons or secure psychiatric facilities where access to alternative intoxicants is more limited. To a significantly greater extent than other atypical antipsychotic drugs, quetiapine was found to be associated with drug-seeking behaviors, and to have standardised street prices and slang terms associated with it, either by itself or in combination with other drugs (such as "Q-ball" for the intravenous injection of quetiapine mixed with cocaine). The pharmacological basis for this distinction from other second generation antipsychotic drugs is unclear, though it has been suggested that quetiapine's comparatively lower dopamine receptor affinity and strong antihistamine activity might mean it could be regarded as more similar to sedating antihistamines in this context. While these issues have not been regarded as sufficient cause for placing quetiapine under increased legal controls, prescribers have been urged to show caution when prescribing quetiapine to individuals with characteristics that might place them at increased risk for drug misuse. [58] [59] [60] [61] [62]
Most instances of acute overdosage result in only sedation, hypotension and tachycardia, but cardiac arrhythmia, coma and death have occurred in adults. Serum or plasma quetiapine concentrations are usually in the 1–10 mg/L range in overdose survivors, while postmortem blood levels of 10–25 mg/L are generally observed in fatal cases. [63] Non-toxic levels in postmortem blood extend to around 0.8 mg/kg, but toxic levels in postmortem blood can begin at 0.35 mg/kg. [64] [65]
Site | QTP | NQTP | Action | Ref |
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SERT | >10,000 | 927 | Blocker | [67] |
NET | >10,000 | 58 | Blocker | [67] |
DAT | >10,000 | >10,000 | ND | [67] |
5-HT1A | 320–432 | 45 | Partial agonist | [67] [68] |
5-HT1B | 1,109–2,050 | 1,117 | ND | [67] [68] |
5-HT1D | >10,000 | 249 | ND | [67] [68] |
5-HT1E | 1,250–2,402 | 97 | ND | [67] [68] |
5-HT1F | 2,240 | ND | ND | [68] |
5-HT2A | 96–101 | 48 | Antagonist | [67] [68] |
5-HT2B | ND | 14 | Antagonist | [67] |
5-HT2C | 2,502 | 107 | Antagonist | [67] |
5-HT3 | >10,000 | 394 | Antagonist | [67] |
5-HT4 | ND | ND | ND | ND |
5-HT5A | 3,120 | 768 | ND | [67] |
5-HT6 | 1,865 | 503 | Antagonist | [67] |
5-HT7 | 307 | 76 | Antagonist | [67] |
α1A | 22 | 144 | Antagonist | [67] |
α1B | 39 | 95 | Antagonist | [67] |
α2A | 2,230–3,630 | 237 | Antagonist | [67] [68] |
α2B | 90–747 | 378 | Antagonist | [67] [68] |
α2C | 28.7–350 | 736 | Antagonist | [67] [68] |
β1 | >10,000 | >10,000 | ND | [67] [68] |
β2 | >10,000 | >10,000 | ND | [67] [68] |
D1 | 712 | 214 | Antagonist | [67] |
D2 | 245 | 196 | Antagonist | [67] |
D2L | 700 | ND | Antagonist | [68] |
D2S | 390 | ND | Antagonist | [68] |
D3 | 340–483 | 567 | Antagonist | [67] [68] |
D4 | 1,202 | 1,297 | Antagonist | [67] |
D4.2 | 1,600 | ND | Antagonist | [68] |
D5 | 1,738 | 1,419 | Antagonist | [67] |
H1 | 2.2–11 | 3.5 | Antagonist | [67] |
H2 | >10,000 | 298 | Antagonist | [67] |
H3 | >10,000 | >10,000 | ND | [67] |
H4 | >10,000 | 1,660 | ND | [67] |
M1 | 858 | 39 | Antagonist | [67] |
M2 | 1,339 | 453 | ND | [67] |
M3 | >10,000 | 23 | Antagonist | [67] |
M4 | 542 | 110 | ND | [67] |
M5 | 1,942 | 23 | Antagonist | [67] |
σ1 | 220–3,651 | >10,000 | ND | [67] [68] |
σ2 | 1,344 | 1,050 | ND | [67] |
NMDA (PCP) | >10,000 | ND | Antagonist | [67] |
VDCC | >10,000 | ND | ND | [67] [68] |
hERG | ND | >10,000 (IC50 ) | ND | [67] |
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site. All data are for human cloned proteins, except σ1 (guinea pig), σ2 (rat), and VDCC (rat). [67] [68] |
Quetiapine has the following pharmacological actions: [69] [70] [71] [72] [4] [73] [74] [75]
This means quetiapine is a dopamine, serotonin, and adrenergic antagonist, and a potent antihistamine with some anticholinergic properties. [76] Quetiapine binds strongly to serotonin receptors; the drug acts as a partial agonist at 5-HT1A receptors and as an antagonist to all other serotonin receptors it has affinity for. [77] Serial PET scans evaluating the D2 receptor occupancy of quetiapine have demonstrated that quetiapine very rapidly disassociates from the D2 receptor. [78] Theoretically, this allows for normal physiological surges of dopamine to elicit normal effects in areas such as the nigrostriatal and tuberoinfundibular pathways, thus minimizing the risk of side-effects such as pseudo-parkinsonism as well as elevations in prolactin. [79] Some of the antagonized receptors (serotonin, norepinephrine) are actually autoreceptors whose blockade tends to increase the release of neurotransmitters.
At very low doses, quetiapine acts primarily as a histamine receptor blocker (antihistamine) and α1-adrenergic blocker. When the dose is increased, quetiapine activates the adrenergic system and binds strongly to serotonin receptors and autoreceptors. At high doses, quetiapine starts blocking significant amounts of dopamine receptors. [70] [80] Due to the drug's sedating H1 activity, it is often prescribed at low doses for insomnia. While some feel that low doses of drugs with antihistamine effects like quetiapine and mirtazapine are safer than drugs associated with physical dependency or other risk factors, concern has been raised by some professionals that off-label prescribing has become too widespread due to underappreciated hazards. [81]
When treating schizophrenia, antagonism of D2 receptor by quetiapine in the mesolimbic pathway relieves positive symptoms and antagonism of the 5-HT2A receptor in the frontal cortex of the brain may relieve negative symptoms and reduce severity of psychotic episodes. [20] [82] [83] Quetiapine has fewer extrapyramidal side effects and is less likely to cause hyperprolactinemia when compared to other drugs used to treat schizophrenia, so is used as a first line treatment. [84] [85]
Peak levels of quetiapine occur 1.5 hours after a dose. [86] The plasma protein binding of quetiapine is 83%. [86] The major active metabolite of quetiapine is norquetiapine (N-desalkylquetiapine). [67] Quetiapine has an elimination half-life of 6 or 7 hours. [86] [7] [9] Its metabolite, norquetiapine, has a half-life of 9 to 12 hours. [7] [9] Quetiapine is excreted primarily via the kidneys (73%) and in feces (20%) after hepatic metabolism, the remainder (1%) is excreted as the drug in its unmetabolized form. [82] [86]
Quetiapine is a tetracyclic compound and is closely related structurally to clozapine, olanzapine, loxapine, and other tetracyclic antipsychotics.
The synthesis of quetiapine begins with a dibenzothiazepinone. The lactam is first treated with phosphoryl chloride to produce a dibenzothiazepine. A nucleophilic substitution is used to introduce the sidechain. [87]
AstraZeneca submitted a new drug application for a sustained-release version of quetiapine in the United States, Canada, and the European Union in the second half of 2006 for treatment of schizophrenia. [88] [89]
In May 2007, the US FDA approved Seroquel XR for acute treatment of schizophrenia. [90] During its 2007 Q2 earnings conference, AstraZeneca announced plans to launch Seroquel XR in the U.S. during August 2007. [91] However, Seroquel XR has become available in U.S. pharmacies only after the FDA approved Seroquel XR for use as maintenance treatment for schizophrenia, in addition to acute treatment of the illness, on 16 November 2007. [92] The company has not provided a reason for the delay of Seroquel XR's launch.
Health Canada approved sale of Seroquel XR on 27 September 2007. [93]
In October 2008, the FDA approved Seroquel XR for the treatment of bipolar depression and bipolar mania.
In December 2008, Biovail announced that the FDA had accepted the company's ANDA to market its own version of sustained-release quetiapine. [94] Biovail's sustained-release tablets will compete with AstraZeneca's Seroquel XR.
In December 2008, AstraZeneca notified shareholders that the FDA had asked for additional information on the company's application to expand the use of sustained-release quetiapine for treatment of depression. [95]
In the United States, the Food and Drug Administration (FDA) has approved quetiapine for the treatment of schizophrenia and of acute manic episodes associated with bipolar disorder (bipolar mania) and for treatment of bipolar depression. [96] In 2009, quetiapine XR was approved as adjunctive treatment of major depressive disorder. [97]
Quetiapine received its initial approval from the US FDA for the treatment of schizophrenia in 1997. [4] [98] In 2004, it received its second indication for the treatment of mania-associated bipolar disorder. [99] In 2007 and 2008, studies were conducted on quetiapine's efficacy in treating generalized anxiety disorder and major depression.
Patent protection for the product ended in 2012; however, in a number of regions, the long-acting version remained under patent until 2017. [100]
In April 2010, the U. S. Department of Justice fined AstraZeneca $520 million for the company's aggressive marketing of Seroquel for off-label uses. [96] According to the Department of Justice, "the company recruited doctors to serve as authors of articles that were ghostwritten by medical literature companies and about studies the doctors in question did not conduct. AstraZeneca then used those studies and articles as the basis for promotional messages about unapproved uses of Seroquel." [96]
Multiple lawsuits have been filed in relation to quetiapine's side-effects, in particular, diabetes. [101] [102] [103] [104]
Approximately 10,000 [105] lawsuits [106] have been filed against AstraZeneca, alleging that quetiapine caused problems ranging from slurred speech and chronic insomnia to deaths.
In 2004, a young man named Dan Markingson committed suicide in a controversial Seroquel clinical trial at the University of Minnesota while under an involuntary commitment order. [107] A group of University of Minnesota bioethicists charged that the trial involved an alarming number of ethical violations. [108]
In August 2011, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) issued a class-4 drug alert following reports that some batches of Nurofen plus contained Seroquel XL tablets instead. [109]
Following the issue of the Class-4 Drug Alert, Reckitt Benckiser (UK) Ltd received further reports of rogue blister strips in cartons of two additional batches of Nurofen Plus tablets. One of the new batches contained Seroquel XL 50 mg tablets and one contained the Pfizer product Neurontin 100 mg capsules.
Following discussions with the MHRA's Defective Medicines Report Centre (DMRC), Reckitt Benckiser (UK) Ltd decided to recall all remaining unexpired stock of Nurofen Plus tablets in any pack size, leading to a Class-1 Drug Alert. [110] The contamination was later traced to in-store tampering by a customer. [111]
Antipsychotics, previously known as neuroleptics and major tranquilizers, 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. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder.
Clozapine, sold under the brand name Clozaril among others, is a psychiatric medication and was the first atypical antipsychotic to be discovered. It is primarily used to treat people with schizophrenia and schizoaffective disorder who have had an inadequate response to two other antipsychotics, or who have been unable to tolerate other drugs due to extrapyramidal side effects. In the US the FDA authorisation also includes use for people with recurrent suicidal behaviour in people with schizophrenia or schizoaffective disorder. It is also used for the treatment of psychosis in Parkinson's disease.
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.
Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as irritability associated with autism. It is taken either by mouth or by injection. The injectable versions are long-acting and last for 2–4 weeks.
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.
Olanzapine, sold under the brand name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. It is also sometimes used off-label for treatment of chemotherapy-induced nausea and vomiting and as an appetite stimulant. 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.
Aripiprazole, sold under the brand names Abilify and Aristada, among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder; other uses include as an add-on treatment in major depressive disorder and obsessive–compulsive disorder (OCD), 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.
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.
Loxapine, sold under the brand names Loxitane and Adasuve among others, is a tricyclic antipsychotic medication used primarily in the treatment of schizophrenia. The medicine is a member of the dibenzoxazepine class and structurally very similar to clozapine. Several researchers have argued that loxapine, initially classified as a typical antipsychotic, behaves as an atypical antipsychotic.
A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.
Chlorprothixene, sold under the brand name Truxal among others, is a typical antipsychotic of the thioxanthene group.
Amisulpride, sold under the brand names Solian and Barhemsys, is a medication used in the treatment of schizophrenia, acute psychotic episodes, depression, and nausea and vomiting. It is specifically used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; at low doses by mouth to treat depression; and at higher doses by mouth to treat psychosis.
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.
Iloperidone, commonly known as Fanapt and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia and bipolar I disorder.
Lurasidone, sold under the brand name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar depression. It is taken by mouth.
Pimavanserin, sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis. It is taken by mouth.
Pomaglumetad (LY-404,039) is an amino acid analog drug that acts as a highly selective agonist for the metabotropic glutamate receptor group II subtypes mGluR2 and mGluR3. Pharmacological research has focused on its potential antipsychotic and anxiolytic effects. Pomaglumetad is intended as a treatment for schizophrenia and other psychotic and anxiety disorders by modulating glutamatergic activity and reducing presynaptic release of glutamate at synapses in limbic and forebrain areas relevant to these disorders. Human studies investigating therapeutic use of pomaglumetad have focused on the prodrug LY-2140023, a methionine amide of pomaglumetad (also called pomaglumetad methionil) since pomaglumetad exhibits low oral absorption and bioavailability in humans.
Cariprazine, sold under the brand name Vraylar among others, is an atypical antipsychotic developed by Gedeon Richter, which is used in the treatment of schizophrenia, bipolar mania, bipolar depression, and major depressive disorder. It acts primarily as a D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Cariprazine is also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors, with high selectivity for the D3 receptor. It is taken by mouth. The most prevalent side effects include nausea, mild sedation, fatigue, and dizziness. At higher dosages, there is an increased risk for restlessness, insomnia, and tremors.
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.
In clinical practice, quetiapine is more readily used than clozapine, given its improved side effect profile compared to clozapine. Despite frequent use in clinical practice, its efficacy in PDP is less clear. ... The quetiapine evidence base is thus ambiguous, lacking consistent support from RCTs in PDP. In DLB there is reliance upon retrospective studies, with the inherent limitations therein. As with clozapine, sedation and orthostasis can be limiting factors. In clinical practice, despite the paucity of consistent evidence, quetiapine has been the first line antipsychotic therapy due to its side effect profile and lower neuroleptic sensitivity risk.
Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.