<unk> s are typically used to treat schizophrenia or bipolar disorder. They are also frequently used to treat agitation associated with dementia, anxiety disorder, autism spectrum disorder, and obsessive-compulsive disorder (an off-label use). In dementia, they should only be considered after other treatments have failed and if the patient is a risk to themselves and/or others. Schizophrenia The first-line psychiatric treatment for schizophrenia is<unk>  medication, which can reduce the positive symptoms of schizophrenia in about 8–15 days.<unk> s only appear to improve secondary negative symptoms of schizophrenia in the short term and may worsen negative symptoms overall. Overall there is no good evidence that<unk> s have any therapeutic benefit for treating the negative symptoms of schizophrenia. There is very little evidence on which to base a risk and benefit assessment of using<unk> s for long-term treatment. The choice of which<unk>  to use for a specific patient is based on benefits, risks, and costs. It is debatable whether, as a class, typical or<unk> s are better. Both have equal drop-out and symptom relapse rates when typicals are used at low to moderate dosages. There is a good response in 40–50% of patients, a partial response in 30–40%, and treatment resistance (failure of symptoms to respond satisfactorily after six weeks to two of three different<unk> s) in the remaining 20%. Clozapine is considered a first choice treatment for treatment resistant schizophrenia, especially in the short term; in the longer-terms the risks of adverse effects complicate the choice. In turn, risperidone, olanzapine, and aripiprazole have been recommended for the treatment of first-episode psychosis. Efficacy in the treatment of schizophrenia The utility of broadly grouping the<unk> s into first generation and atypical categories has been challenged. It has been argued that a more nuanced view, matching the properties of individual drugs to the needs of specific patients is preferable. While the atypical (second-generation)<unk> s were marketed as offering greater efficacy in reducing psychotic symptoms while reducing side effects (and extrapyramidal symptoms in particular) than typical medications, the results showing these effects often lacked robustness, and the assumption was increasingly challenged even as atypical prescriptions were soaring. In 2005 the US government body NIMH published the results of a major independent (not funded by the pharmaceutical companies) multi-site, double-blind study (the CATIE project). This study compared several<unk> s to an older, mid-potency<unk> , perphenazine, among 1,493 persons with schizophrenia. The study found that only olanzapine outperformed perphenazine in discontinuation rate (the rate at which people stopped taking it due to its effects). The authors noted an apparent superior efficacy of olanzapine to the other drugs in terms of reduction in psychopathology and rate of hospitalizations, but olanzapine was associated with relatively severe metabolic effects such as a major weight gain problem (averaging 9.4 lbs over 18 months) and increases in glucose, cholesterol, and triglycerides. No other atypical studied (risperidone, quetiapine, and ziprasidone) did better than the typical perphenazine on the measures used, nor did they produce fewer adverse effects than the<unk>  perphenazine (a result supported by a meta-analysis by Leucht et al. published in The Lancet), although more patients discontinued perphenazine owing to extrapyramidal effects compared to the atypical agents (8% vs. 2% to 4%, P=0.002). A phase 2 part of this CATIE study roughly replicated these findings. Compliance has not been shown to be different between the two types. Overall evaluations of the CATIE and other studies have led many researchers to question the first-line prescribing of atypicals over typicals, or even to question the distinction between the two classes. It has been suggested that there is no validity to the term "second-generation<unk>  drugs" and that the drugs that currently occupy this category are not identical to each other in mechanism, efficacy, and side-effect profiles. Bipolar disorder In bipolar disorder, SGAs are most commonly used to rapidly control acute mania and mixed episodes, often in conjunction with mood stabilizers (which tend to have a delayed onset of action in such cases) such as lithium and valproate. In milder cases of mania or mixed episodes, mood stabilizer monotherapy may be attempted first. SGAs are also used to treat other aspects of the disorder (such as acute bipolar depression or as a prophylactic treatment) as adjuncts or as a monotherapy, depending on the drug. Both quetiapine and olanzapine have demonstrated significant efficacy in all three treatment phases of bipolar disorder. Lurasidone (trade name Latuda) has demonstrated some efficacy in the acute depressive phase of bipolar disorder. Major depressive disorder In non-psychotic major depressive disorder (MDD), some SGAs have demonstrated significant efficacy as adjunctive agents; and, such agents include: * Aripiprazole *Brexpiprazole * Olanzapine * Quetiapine * Ziprasidone whereas only quetiapine has demonstrated efficacy as a monotherapy in non-psychotic MDD. Olanzapine/fluoxetine is an efficacious treatment in both psychotic and non-psychotic MDD. Aripiprazole, brexpiprazole, olanzapine, and quetiapine have been approved as adjunct treatment for MDD by the FDA in the United States. Quetiapine and lurasidone have been approved, as monotherapies, for bipolar depression, but as of present, lurasidone has not been approved for MDD. Autism Both risperidone and aripiprazole have received FDA approval for irritability in autism. Dementia and Alzheimer's disease Between May 2007 and April 2008, Dementia and Alzheimer's together accounted for 28% of<unk>  use in patients aged 65 or older. The U.S. Food and Drug Administration requires that all<unk> s carry a black box warning that the medication has been associated with an increased risk of mortality in elderly patients. In 2005, the FDA issued an advisory warning of an increased risk of death when<unk> s are used in dementia. In the subsequent 5 years, the use of<unk> s to treat dementia decreased by nearly 50%. Comparison table of efficacy Generic Drug Name Schizophrenia Mania Bipolar Maintenance Bipolar Depression Adjunct in Major Depressive Disorder Amisulpride +++ ? ? ? ? (+++ as a dysthymia monotherapy, however) Aripiprazole ++ ++ ++/+ - +++ Asenapine +++ ++ ++ ? (some evidence has suggested efficacy in treating depressive symptoms in mixed/manic episodes) ? Blonanserin ++ ? ? ? ? Cariprazine +++ ? ? ? ? Clozapine +++ ? ? ? ? Iloperidone + ? ? ? ? Lurasidone + ? ? +++ ? Melperone +++/++ ? ? ? ? Olanzapine +++ +++ ++ +++/++ (+++ when combined with fluoxetine) ++ Paliperidone ++ ? ? ? ? Perospirone + ? ? ? ? Quetiapine ++ ++ +++ ++ ++ Risperidone +++ +++ ++ - + Sertindole ++ ? ? ? ? Ziprasidone ++/+ ++/+ ? - ? Zotepine ++ ? ? ? ? Legend: :- Inefficacious :+ Less effective than most treatments, but still with some efficacy. :++ Standard, in terms of efficacy, treatment. No convincing evidence to say it is superior to other standard treatments. :+++ Very efficacious agent. The efficacy of this treatment in the indication in question has been proven to be significantly greater than many other treatments.
Atypical antipsychotic
Atypical antidepressant
Tricyclic antidepressant
Tetracyclic antidepressant
Heterocyclic antidepressant
Typical antipsychotic
Second-generation antidepressant
Antipsychotic