Antipsychotics are most frequently used for the following conditions: •
Schizophrenia •
Psychotic depression. In this indication it is a common practice for the psychiatrist to prescribe a
combination of an atypical antipsychotic and an antidepressant as this practice is best supported by the evidence. The same can be said for
insomnia, in which they are not recommended as first-line therapy.
Aripiprazole, an
atypical antipsychotic, is used as add-on medication to ameliorate sexual dysfunction as a symptom of
selective serotonin reuptake inhibitor (SSRI) antidepressants in women.
Quetiapine is used to treat
generalized anxiety disorder.
Schizophrenia Antipsychotic drug treatment is a key component of
schizophrenia treatment recommendations by the
National Institute of Health and Care Excellence (NICE), the
American Psychiatric Association, and the British Society for Psychopharmacology. The main aim of treatment with antipsychotics is to reduce the
positive symptoms of psychosis, that include delusions and hallucinations. In general, the efficacy of antipsychotic treatment in reducing positive symptoms appears to increase with the severity of baseline symptoms. All antipsychotic medications work relatively the same way: by antagonizing D2 dopamine receptors. However, there are some differences when it comes to typical and atypical antipsychotics. For example, atypical antipsychotic medications have been seen to lower the neurocognitive impairment associated with schizophrenia more than conventional antipsychotics, although the reasoning and mechanics of this are still unclear to researchers. Applications of antipsychotic drugs in the treatment of schizophrenia include
prophylaxis for those showing symptoms that suggest that they are at high risk of developing psychosis; treatment of first-episode psychosis;
maintenance therapy (a form of prophylaxis, maintenance therapy aims to maintain therapeutic benefit and prevent symptom relapse); and treatment of recurrent episodes of acute psychosis. Researchers analyzed data from 32,240 individuals aged 17 to 64 diagnosed with schizophrenia between 2002 and 2012 to arrive at this conclusion.
Prevention of psychosis and symptom improvement Test batteries such as the PACE (Personal Assessment and Crisis Evaluation Clinic) and COPS (Criteria of Prodromal Syndromes), which measure low-level psychotic symptoms and cognitive disturbances, are used to evaluate people with early, low-level symptoms of psychosis. Test results are combined with
family history information to identify patients in the "high-risk" group; they are considered to have a 20–40% risk of progression to frank psychosis within two years.
First-episode psychosis First-episode psychosis (FEP) is the first time that psychotic symptoms are presented. NICE recommends that all people presenting with first-episode psychosis be treated with both an antipsychotic drug and
cognitive behavioral therapy (CBT). NICE further recommends that those expressing a preference for CBT alone be informed that combination treatment is more effective. The conversion rate for a first episode of
drug induced psychosis to bipolar disorder or schizophrenia is lower, with 30% of people converting to either bipolar disorder or schizophrenia. NICE makes no distinction between substance-induced psychosis and any other form of psychosis. The rate of conversion differs for different classes of drugs. The goals of treatment for FEP include reducing symptoms and potentially improving long-term treatment outcomes.
Randomized clinical trials have provided evidence for the efficacy of antipsychotic drugs in achieving the former goal, with first-generation and second generation antipsychotics showing about equal efficacy. The evidence that early treatment has a favorable effect on long-term outcomes is equivocal. There is little or no difference in efficacy among approved antipsychotic drugs, including both first- and second-generation agents. The efficacy of such drugs is suboptimal. Few patients achieve complete resolution of symptoms. Response rates, calculated using various cutoff values for symptom reduction, are low, and their interpretation is complicated by high placebo response rates and selective publication of clinical trial results.
Maintenance therapy The majority of patients treated with an antipsychotic drug will experience a response within four weeks. The goals of continuing treatment are to maintain suppression of symptoms, prevent relapse, improve quality of life, and support engagement in psychosocial therapy. A 3-year trial following persons receiving maintenance therapy after an acute psychotic episode found that 33% obtained long-lasting symptom reduction, 13% achieved remission, and only 27% experienced satisfactory quality of life. The effect of relapse prevention on long term outcomes is uncertain, as historical studies show little difference in long term outcomes before and after the introduction of antipsychotic drugs. The authors speculated that the difference may be because the people that discontinued treatment after a longer time had more severe mental illness than those that discontinued antipsychotic therapy sooner. If someone experiences psychotic symptoms due to nonadherence, they may be compelled to receive treatment through a process called
involuntary commitment, in which they can be forced to accept treatment (including antipsychotics). A person can also be committed to treatment outside of a hospital, called
outpatient commitment. Antipsychotics in
long-acting injectable (LAI), or "depot", form have been suggested as a method of decreasing medication nonadherence (sometimes also called non-compliance). NICE advises LAIs be offered to patients when preventing covert, intentional nonadherence is a clinical priority. LAIs are used to ensure adherence in outpatient commitment. A meta-analysis found that LAIs resulted in lower rates of rehospitalization with a hazard ratio of 0.83; however, these results were not statistically significant (the 95% confidence interval was 0.62 to 1.11). The reason for this combination is the therapeutic delay of the aforementioned mood stabilizers (for valproate therapeutic effects are usually seen around five days after treatment is commenced whereas lithium usually takes at least a week The antipsychotics have a documented efficacy when used alone in acute mania/mixed episodes.
cariprazine,
lurasidone,
olanzapine, and
quetiapine) have also been found to possess efficacy in the treatment of bipolar depression as a monotherapy, whereas only olanzapine and quetiapine have been proven to be effective broad-spectrum (i.e., against all three types of relapse—manic, mixed and depressive) prophylactic (or
maintenance) treatments in patients with bipolar disorder. A recent Cochrane review also found that olanzapine had a less favourable risk/benefit ratio than
lithium as a maintenance treatment for bipolar disorder. The
American Psychiatric Association and the UK
National Institute for Health and Care Excellence recommend antipsychotics for managing acute psychotic episodes in schizophrenia or bipolar disorder, and as a longer-term maintenance treatment for reducing the likelihood of further episodes. They state that response to any given antipsychotic can be variable so that trials may be necessary, and that lower doses are to be preferred where possible. A number of studies have looked at levels of "compliance" or "adherence" with antipsychotic regimes and found that discontinuation (stopping taking them) by patients is associated with higher rates of relapse, including hospitalization.
Dementia Psychosis and agitation develop in as many as 80 percent of people living in nursing homes. Antipsychotics in old age dementia showed a modest benefit compared to placebo in managing aggression or psychosis, but this is combined with a fairly large increase in serious adverse events. Thus, antipsychotics should not be used routinely to treat dementia with aggression or psychosis, but may be an option in a few cases where there is severe distress or risk of physical harm to others. Psychosocial interventions may reduce the need for antipsychotics. In 2005, the FDA issued an advisory warning of an increased risk of death when atypical antipsychotics are used in dementia. In the subsequent 5 years, the use of atypical antipsychotics to treat dementia decreased by nearly 50%.
Aripiprazole,
quetiapine extended-release, and
olanzapine (when used in conjunction with
fluoxetine) have received the
Food and Drug Administration (FDA) labelling for this indication. There is, however, a greater risk of side effects with their use compared to using traditional antidepressants. A recent study on the use of antipsychotics in
unipolar depression concluded that the use of those drugs in addition to
antidepressants alone leads to a worse disease outcome. This effect is especially pronounced in younger patients with psychotic unipolar depression. Considering the wide use of such combination therapies, further studies on the side effects of antipychotics as an add-on therapy are warranted.
Other Global antipsychotic utilization has seen a steady growth since the introduction of atypical (second-generation) antipsychotics and this is ascribed to off-label use for many other unapproved disorders. Besides the above uses antipsychotics may be used for
obsessive–compulsive disorder,
post-traumatic stress disorder,
personality disorders,
Tourette syndrome,
autism and agitation in those with dementia. The atypical antipsychotic
risperidone may be useful for
obsessive–compulsive disorder. The use of low doses of antipsychotics for
insomnia, while common, is not recommended as there is little evidence of benefit as well as concern regarding adverse effects. Some of the more serious adverse effects may also occur at the low doses used, such as
dyslipidemia and
neutropenia, and a recent network meta-analysis of 154 double-blind, randomized controlled trials of drug therapies vs. placebo for insomnia in adults found that quetiapine did not demonstrated any short-term benefits in sleep quality. Low dose antipsychotics may also be used in treatment of impulse-behavioural and cognitive-perceptual symptoms of
borderline personality disorder. Despite the lack of evidence supporting the benefit of antipsychotics in people with personality disorders, 1 in 4 who do not have a
serious mental illness are prescribed them in UK
primary care. Many people receive these medication for over a year, contrary to
NICE guidelines. In children they may be used in those with
disruptive behavior disorders,
mood disorders and
pervasive developmental disorders or
intellectual disability. Antipsychotics are only weakly recommended for Tourette syndrome, because although they are effective, side effects are common. The situation is similar for those on the
autism spectrum. Much of the evidence for the off-label use of antipsychotics (for example, for dementia, OCD, PTSD, personality disorders, Tourette's) was of insufficient scientific quality to support such use, especially as there was strong evidence of increased risks of stroke, tremors, significant weight gain, sedation, and gastrointestinal problems. A UK review of unlicensed usage in children and adolescents reported a similar mixture of findings and concerns. A survey of children with
pervasive developmental disorder found that 16.5% were taking an antipsychotic drug, most commonly for irritability, aggression, and agitation. Both
risperidone and
aripiprazole have been approved by the US FDA for the treatment of irritability in autistic children and adolescents. A review in the UK found that the use of antipsychotics in England doubled between 2000 and 2019. Children were prescribed antipsychotics for conditions for which there is no approval, such as autism. Aggressive challenging behavior in adults with
intellectual disability is often treated with antipsychotic drugs despite lack of an evidence base. A recent
randomized controlled trial, however, found no benefit over
placebo and recommended that the use of antipsychotics in this way should no longer be regarded as an acceptable routine treatment. Antipsychotics may be an option, together with stimulants, in people with ADHD and aggressive behavior when other treatments have not worked, however, they have predominantly opposing effects and may have additive cardiovascular risks when used together. They have not been found to be useful for the prevention of
delirium among those admitted to hospital. A 2019 study using national prescribing data found that antipsychotics were prescribed to a significant minority of youth with
attention deficit hyperactivity disorder (ADHD), frequently without FDA-approved indications and in cases where stimulant medications had not been tried first, raising concerns about guideline adherence in pediatric treatment.
Typicals vs atypicals Aside from reduced extrapyramidal symptoms, and with the clear exception of clozapine, it is unclear whether the
atypical (second-generation) antipsychotics offer advantages over older, first generation antipsychotics.
Amisulpride,
olanzapine,
risperidone and
clozapine may be more effective but are associated with greater side effects. Typical antipsychotics have equal drop-out and symptom relapse rates to atypicals when used at low to moderate dosages. Clozapine is an effective treatment for those who respond poorly to other drugs ("treatment-resistant" or "refractory" schizophrenia), but it has the potentially serious side effect of
agranulocytosis (lowered
white blood cell count) in less than 4% of people. Due to bias in the research the accuracy of comparisons of atypical antipsychotics is a concern. In 2005, a US government body, the
National Institute of Mental Health published the results of a major independent study (the CATIE project). No other atypical studied (
risperidone,
quetiapine, and
ziprasidone) did better than the first-generation antipsychotic perphenazine on the measures used, nor did they produce fewer adverse effects than the typical antipsychotic perphenazine, although more patients discontinued perphenazine owing to
extrapyramidal effects compared to the atypical agents (8% vs. 2% to 4%). This is significant because any patient with tardive dyskinesia was specifically excluded from randomization to perphenazine; i.e., in the CATIE study the patient cohort randomized to receive perphenazine was at lower risk of having extrapyramidal symptoms. Atypical antipsychotics do not appear to lead to improved rates of medication adherence compared to typical antipsychotics. Many researchers question the first-line prescribing of atypicals over typicals, and some even question the distinction between the two classes. In contrast, other researchers point to the significantly higher risk of
tardive dyskinesia and other extrapyramidal symptoms with the typicals and for this reason alone recommend first-line treatment with the atypicals, notwithstanding a greater propensity for metabolic adverse effects in the latter. The UK government organization
NICE recently revised its recommendation favoring atypicals, to advise that the choice should be an individual one based on the particular profiles of the individual drug and on the patient's preferences. The re-evaluation of the evidence has not necessarily slowed the bias toward prescribing the atypicals. ==Other uses==