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antipsychotic
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factoids
| Biological_target =}}Antipsychotics, also known as neuroleptics or major tranquilizers,BOOK, Finkel, Richard Finkel, Clark, Michelle Alexia, Cubeddu, Luigi X., vanc, Pharmacology, 2009, Lippincott Williams & Wilkins, 9780781771559, 151,weblink en, live,weblink 1 April 2017, dmy-all, are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. Antipsychotics are usually effective in relieving symptoms of psychosis in the short term.
The long-term use of antipsychotics is associated with adverse effects such as involuntary movement disorders, gynecomastia, impotence, weight gain and metabolic syndrome.First-generation antipsychotics, known as typical antipsychotics, were discovered in the 1950s. Most second-generation drugs, known as atypical antipsychotics, have been developed more recently, although the first atypical antipsychotic, clozapine, was discovered in the 1960s and introduced clinically in the 1970s.JOURNAL, Hippius, H., 1989-03-01, The history of clozapine, Psychopharmacology, en, 99, 1, S3–S5, 10.1007/BF00442551, 2682730, 0033-3158, Both generations of medication tend to block receptors in the brain's dopamine pathways, but atypicals tend to act on serotonin receptors as well. Neuroleptic, originating from (neuron) and (take hold of) – thus meaning "which takes the nerve" – refers to both common neurological effects and side effects.JOURNAL, King C, Voruganti LN, What's in a name? The evolution of the nomenclature of antipsychotic drugs, Journal of Psychiatry & Neuroscience, 27, 3, 168–75, May 2002, 12066446, 161646, {{TOC limit|3}}

Medical uses

Antipsychotics are most frequently used for the following conditions:
  • Schizophrenia
  • Schizoaffective disorder most commonly in conjunction with either an antidepressant (in the case of the depressive subtype) or a mood stabiliser (in the case of the bipolar subtype).
  • Bipolar disorder (acute mania and mixed episodes) may be treated with either typical or atypical antipsychotics, although atypical antipsychotics are usually preferred because they tend to have more favourable adverse effect profiles and, according to a recent meta-analysis, they tend to have a lower liability for causing conversion from mania to depression.JOURNAL, Goikolea JM, Colom F, Torres I, Capapey J, Valentí M, Undurraga J, Grande I, Sanchez-Moreno J, Vieta E, Lower rate of depressive switch following antimanic treatment with second-generation antipsychotics versus haloperidol, Journal of Affective Disorders, 144, 3, 191–8, January 2013, 23089129, 10.1016/j.jad.2012.07.038,
  • 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.
  • Treatment-resistant (and not necessarily psychotic) major depression as an adjunct to standard antidepressant therapy.
They are not recommended for dementia or insomnia unless other treatments have not worked. They are not recommended in children unless other treatments are not effective or unless the child has psychosis.WEB, American Psychiatric Association Five Things Physicians and Patients Should Question,weblink Choosing Wisely, 23 September 2013, live,weblink" title="web.archive.org/web/20131203174206weblink">weblink 3 December 2013, dmy-all, The World Health Organization provides a description of recommendations for the prescription of antipsychotics for the purposes of the treatment of psychosis.Antipsychotic medications for psychotic disorders {{webarchive|url=https://web.archive.org/web/20171020013941weblink |date=20 October 2017 }} World Health Organization 2012 Accessed October 12th, 2017

Schizophrenia

Antipsychotic drug treatment is a key component of schizophrenia treatment algorithms recommended by the National Institute of Health and Care Excellence (NICE),WEB,weblink Psychosis and schizophrenia in adults (CG178), live,weblink" title="web.archive.org/web/20140304005556weblink">weblink 4 March 2014, dmy-all, the American Psychiatric Association,WEB,weblink PsychiatryOnline | Guidelines, and the British Society for Psychopharmacology.JOURNAL, Barnes TR, Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology, Journal of Psychopharmacology, 25, 5, 567–620, May 2011, 21292923, 10.1177/0269881110391123, The main effect of treatment with antipsychotics is to reduce the so-called "positive" symptoms, including delusions and hallucinations. There is mixed evidence to support a significant impact of antipsychotic use on negative symptoms (such as apathy, lack of emotional affect, and lack of interest in social interactions) or on the cognitive symptoms (disordered thinking, reduced ability to plan and execute tasks) of schizophrenia.JOURNAL, Miyamoto S, Miyake N, Jarskog LF, Fleischhacker WW, Lieberman JA, Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents, Molecular Psychiatry, 17, 12, 1206–27, December 2012, 22584864, 10.1038/mp.2012.47, JOURNAL, Hartling L, Abou-Setta AM, Dursun S, Mousavi SS, Pasichnyk D, Newton AS, Antipsychotics in adults with schizophrenia: comparative effectiveness of first-generation versus second-generation medications: a systematic review and meta-analysis, Annals of Internal Medicine, 157, 7, 498–511, October 2012, 22893011, 10.7326/0003-4819-157-7-201210020-00525, In general, the efficacy of antipsychotic treatment in reducing both positive and negative symptoms appears to increase with increasing severity of baseline symptoms.JOURNAL, Furukawa TA, Levine SZ, Tanaka S, Goldberg Y, Samara M, Davis JM, Cipriani A, Leucht S, Initial severity of schizophrenia and efficacy of antipsychotics: participant-level meta-analysis of 6 placebo-controlled studies, JAMA Psychiatry, 72, 1, 14–21, January 2015, 25372935, 10.1001/jamapsychiatry.2014.2127, 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 so than conventional antipsychotics, although the reasoning and mechanics of this are still unclear to researchers.JOURNAL, Keefe RS, Silva SG, Perkins DO, Lieberman JA, The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis, Schizophrenia Bulletin, 25, 2, 201–22, 1999-01-01, 10416727, 10.1093/oxfordjournals.schbul.a033374, Applications of antipsychotic drugs in the treatment of schizophrenia include prophylaxis in those showing symptoms that suggest that they are at high risk of developing psychosis, treatment of first episode psychosis, maintenance therapy, and treatment of recurrent episodes of acute psychosis.

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 others focused on cognitive disturbances (Basic symptoms"), are used to evaluate people with early, low level symptoms of psychosis. Used in combination with family history information, these tests can identify a "high risk" group having a 20–40% risk of progression to frank psychosis within 2 years. These patients are often treated with low doses of antipsychotic drugs with the goal of reducing their symptoms and preventing progression to frank psychosis. While generally useful for reducing symptoms, the clinical trials performed to date provide little evidence that early use of antipsychotics, alone or in combination with cognitive-behavioral therapy, provides improved long term outcomes in those with prodromal symptoms.WEB,weblink NICE Treatment Guidance 2014, 2014-08-07, live,weblink" title="web.archive.org/web/20140813081133weblink">weblink 13 August 2014, dmy-all,

First episode psychosis

NICE recommends that all persons presenting with a first episode of frank 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 efficacious. A diagnosis of schizophrenia is not normally made at this time, as up to 25% of those presenting with first episode psychosis are eventually found to suffer from bipolar disorder instead. The goals of treatment of these patients 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. Evidence that early treatment has a favorable effect on long term outcomes is equivocal.

Recurrent psychotic episodes

Placebo-controlled trials of both first and second generation antipsychotic drugs consistently demonstrate the superiority of active drug to placebo in suppressing psychotic symptoms. A large meta-analysis of 38 trials of antipsychotic drugs in schizophrenia acute psychotic episodes showed an effect size of about 0.5.JOURNAL, Leucht S, Arbter D, Engel RR, Kissling W, Davis JM, How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials, Molecular Psychiatry, 14, 4, 429–47, April 2009, 18180760, 10.1038/sj.mp.4002136, There is little or no difference in efficacy among approved antipsychotic drugs, including both first- and second-generation agents.JOURNAL, Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM, Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis, Lancet, 382, 9896, 951–62, September 2013, 23810019, 10.1016/S0140-6736(13)60733-3, 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.JOURNAL, Beitinger R, Lin J, Kissling W, Leucht S, Comparative remission rates of schizophrenic patients using various remission criteria, Progress in Neuro-Psychopharmacology & Biological Psychiatry, 32, 7, 1643–51, October 2008, 18616969, 10.1016/j.pnpbp.2008.06.008,

Maintenance therapy

The majority of patients treated with an antipsychotic drug will experience a response within 4 weeks. The goals of continuing treatment are to maintain suppression of symptoms, prevent relapse, improve quality of life, and support engagement in psychosocial therapy.Maintenance therapy with antipsychotic drugs is clearly superior to placebo in preventing relapse, but is associated with weight gain, movement disorders, and high dropout rates.JOURNAL, Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Davis JM, Maintenance treatment with antipsychotic drugs for schizophrenia, The Cochrane Database of Systematic Reviews, 5, 5, CD008016, May 2012, 22592725, 10.1002/14651858.CD008016.pub2, 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.A significant challenge in the use of antipsychotic drugs for the prevention of relapse is the poor rate of compliance. In spite of the relatively high rates of adverse effects associated with these drugs, some evidence, including higher dropout rates in placebo arms compared to treatment arms in randomized clinical trials, suggest that most patients who discontinue treatment do so because of suboptimal efficacy.JOURNAL, Kinon BJ, Ascher-Svanum H, Adams DH, Chen L, The temporal relationship between symptom change and treatment discontinuation in a pooled analysis of 4 schizophrenia trials, Journal of Clinical Psychopharmacology, 28, 5, 544–9, October 2008, 18794651, 10.1097/JCP.0b013e318185e74a,

Bipolar disorder

Antipsychotics are routinely used, often in conjunction with mood stabilisers such as lithium/valproate, as a first-line treatment for manic and mixed episodes associated with bipolar disorder.BOOK, Taylor D, Paton C, Kapur S, Taylor D, The Maudsley prescribing guidelines in psychiatry, 2012, Wiley-Blackwell, Chichester, West Sussex, UK, 978-0-470-97948-8, 11th, BOOK, Young LL, Kradjan WA, Guglielmo BJ, Corelli RL, Williams BR, Koda-Kimble MA, Applied therapeutics: the clinical use of drugs, 2009, Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, 978-0-7817-6555-8, 3040, 9th, The reason for this combination is the therapeutic delay of the aforementioned mood stabilisers (for valproate therapeutic effects are usually seen around five days after treatment is commenced whereas lithium usually takes at least a week before the full therapeutic effects are seen) and the comparatively rapid antimanic effects of antipsychotic drugs.JOURNAL, Correll CU, Sheridan EM, DelBello MP, Antipsychotic and mood stabilizer efficacy and tolerability in pediatric and adult patients with bipolar I mania: a comparative analysis of acute, randomized, placebo-controlled trials, Bipolar Disorders, 12, 2, 116–41, March 2010, 20402706, 10.1111/j.1399-5618.2010.00798.x, The antipsychotics have a documented efficacy when used alone in acute mania/mixed episodes.Three atypical antipsychotics (lurasidone,WEB,weblink Lurasidone Approved for Bipolar Depression, Lowes R, Medscape, 2013-10-02, live,weblink" title="web.archive.org/web/20131002013831weblink">weblink 2 October 2013, dmy-all, olanzapineJOURNAL, Tohen M, Katagiri H, Fujikoshi S, Kanba S, Efficacy of olanzapine monotherapy in acute bipolar depression: a pooled analysis of controlled studies, Journal of Affective Disorders, 149, 1–3, 196–201, July 2013, 23485111, 10.1016/j.jad.2013.01.022, and quetiapineJOURNAL, Thase ME, Quetiapine monotherapy for bipolar depression, Neuropsychiatric Disease and Treatment, 4, 1, 11–21, February 2008, 18728771, 2515925, 10.2147/ndt.s1162, ) have also been found to possess efficacy in the treatment of bipolar depression as a monotherapy, whereas only olanzapineJOURNAL, Tohen M, Greil W, Calabrese JR, Sachs GS, Yatham LN, Oerlinghausen BM, Koukopoulos A, Cassano GB, Grunze H, Licht RW, Dell'Osso L, Evans AR, Risser R, Baker RW, Crane H, Dossenbach MR, Bowden CL, Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial, The American Journal of Psychiatry, 162, 7, 1281–90, July 2005, 15994710, 10.1176/appi.ajp.162.7.1281, and quetiapineJOURNAL, Duffy A, Milin R, Grof P, Maintenance treatment of adolescent bipolar disorder: open study of the effectiveness and tolerability of quetiapine, BMC Psychiatry, 9, 4, February 2009, 19200370, 2644292, 10.1186/1471-244X-9-4, JOURNAL, Weisler RH, Nolen WA, Neijber A, Hellqvist A, Paulsson B, Continuation of quetiapine versus switching to placebo or lithium for maintenance treatment of bipolar I disorder (Trial 144: a randomized controlled study), The Journal of Clinical Psychiatry, 72, 11, 1452–64, November 2011, 22054050, 10.4088/JCP.11m06878, 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.JOURNAL, Cipriani A, Rendell JM, Geddes J, Olanzapine in long-term treatment for bipolar disorder, The Cochrane Database of Systematic Reviews, 1, CD004367, January 2009, 19160237, 10.1002/14651858.CD004367.pub2, Cipriani, Andrea, 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.JOURNAL, Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, Kreyenbuhl J, Practice guideline for the treatment of patients with schizophrenia, second edition, The American Journal of Psychiatry, 161, 2 Suppl, 1–56, February 2004, 15000267, The Royal College of Psychiatrists & The British Psychological Society (2003).Schizophrenia. Full national clinical guideline on core interventions in primary and secondary care (PDF). London: Gaskell and the British Psychological Society.{{page needed|date=July 2013}} {{webarchive |url=https://web.archive.org/web/20070927014932weblink |date=27 September 2007 }} 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

An assessment for an underlying cause of behavior is needed before prescribing antipsychotic medication for symptoms of dementia.{{Citation |author1 = AMDA – The Society for Post-Acute and Long-Term Care Medicine |author1-link = AMDA – The Society for Post-Acute and Long-Term Care Medicine |date = February 2014 |title = Ten Things Physicians and Patients Should Question |publisher = AMDA – The Society for Post-Acute and Long-Term Care Medicine |work = Choosing Wisely: an initiative of the ABIM Foundation |page = |url =weblink |accessdate = 20 April 2015 |url-status = live|archiveurl =weblink" title="web.archive.org/web/20140913011101weblink">weblink |archivedate = 13 September 2014 |df = dmy-all }}. 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.JOURNAL, Ballard C, Waite J, The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease, The Cochrane Database of Systematic Reviews, 1, CD003476, January 2006, 16437455, 10.1002/14651858.CD003476.pub2, Ballard, Clive G, Psychosocial interventions may reduce the need for antipsychotics.JOURNAL, Richter T, Meyer G, Möhler R, Köpke S, Psychosocial interventions for reducing antipsychotic medication in care home residents, The Cochrane Database of Systematic Reviews, 12, CD008634, December 2012, 23235663, 6492452, 10.1002/14651858.CD008634.pub2, Köpke, Sascha,

Unipolar depression

A number of atypical antipsychotics have some benefits when used in addition to other treatments in major depressive disorder.JOURNAL, Komossa K, Depping AM, Gaudchau A, Kissling W, Leucht S, Second-generation antipsychotics for major depressive disorder and dysthymia, The Cochrane Database of Systematic Reviews, 12, CD008121, December 2010, 21154393, 10.1002/14651858.CD008121.pub2, JOURNAL, Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC, Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes, PLoS Medicine, 10, 3, e1001403, 2013, 23554581, 3595214, 10.1371/journal.pmed.1001403, Aripiprazole, quetiapine, and olanzapine (when used in conjunction with fluoxetine) have received the Food and Drug Administration (FDA) labelling for this indication.Truven Health Analytics, Inc. DrugPoint System (Internet) [cited 2013 Oct 2]. Greenwood Village, CO: Thomsen Healthcare; 2013. There is, however, a greater risk of side effects with their use.

Other

Besides the above uses antipsychotics may be used for obsessive–compulsive disorder, posttraumatic stress disorder, personality disorders, Tourette syndrome, autism and agitation in those with dementia. Evidence however does not support the use of atypical antipsychotics in eating disorders or personality disorder.BOOK, vanc, Maglione M, Maher AR, Hu J, Wang Z, Shanman R, Shekelle PG, Roth B, Hilton L, Suttorp MJ, 2011, Off-Label Use of Atypical Antipsychotics: An Update, Comparative Effectiveness Reviews, No. 43, Rockville, Agency for Healthcare Research and Quality, 22973576, Risperidone may be useful for obsessive–compulsive disorder.JOURNAL, Maher AR, Theodore G, Summary of the comparative effectiveness review on off-label use of atypical antipsychotics, Journal of Managed Care Pharmacy, 18, 5 Suppl B, S1–20, June 2012, 22784311, 10.18553/jmcp.2012.18.s5-b.1, The use of low doses of antipsychotics for insomnia, while common, is not recommended as there is little evidence of benefit and concerns regarding adverse effects.JOURNAL, Coe HV, Hong IS, Safety of low doses of quetiapine when used for insomnia, The Annals of Pharmacotherapy, 46, 5, 718–22, May 2012, 22510671, 10.1345/aph.1Q697, Low dose antipsychotics may also be used in treatment of impulse-behavioural and cognitive-perceptual symptoms of borderline personality disorder.BOOK, vanc, American Psychiatric Association and American Psychiatric Association. Work Group on Borderline Personality Disorder, Practice Guideline for the Treatment of Patients With Borderline Personality Disorder,weblink June 5, 2013, 2001, American Psychiatric Pub, 4, 978-0890423196, In children they may be used in those with disruptive behavior disorders, mood disorders and pervasive developmental disorders or intellectual disability.JOURNAL, Zuddas A, Zanni R, Usala T, Second generation antipsychotics (SGAs) for non-psychotic disorders in children and adolescents: a review of the randomized controlled studies, European Neuropsychopharmacology, 21, 8, 600–20, August 2011, 21550212, 10.1016/j.euroneuro.2011.04.001, Antipsychotics are only weakly recommended for Tourette syndrome, because although they are effective, side effects are common.JOURNAL, Pringsheim T, Doja A, Gorman D, McKinlay D, Day L, Billinghurst L, Carroll A, Dion Y, Luscombe S, Steeves T, Sandor P, Canadian guidelines for the evidence-based treatment of tic disorders: pharmacotherapy, Canadian Journal of Psychiatry, 57, 3, 133–43, March 2012, 22397999, 10.1177/070674371205700302, The situation is similar for those on the autism spectrum.JOURNAL, McPheeters ML, Warren Z, Sathe N, Bruzek JL, Krishnaswami S, Jerome RN, Veenstra-Vanderweele J, A systematic review of medical treatments for children with autism spectrum disorders, Pediatrics, 127, 5, e1312–21, May 2011, 21464191, 10.1542/peds.2011-0427, 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.PRESS RELEASE, Evidence Lacking to Support Many Off-label Uses of Atypical Antipsychotics, Agency for Healthcare Research and Quality, January 17, 2007,weblink July 29, 2013, live,weblink" title="web.archive.org/web/20130225052120weblink">weblink 25 February 2013, dmy-all, A UK review of unlicensed usage in children and adolescents reported a similar mixture of findings and concerns.JOURNAL, 10.1192/apt.bp.108.005652, Prescribing antipsychotics for children and adolescents, 2010, James AC, Advances in Psychiatric Treatment, 16, 1, 63–75, A survey of children with pervasive developmental disorder found that 16.5% were taking an antipsychotic drug, most commonly for irritability, aggression, and agitation. Risperidone has been approved by the US FDA for the treatment of irritability in autistic children and adolescents.JOURNAL, Posey DJ, Stigler KA, Erickson CA, McDougle CJ, Antipsychotics in the treatment of autism, The Journal of Clinical Investigation, 118, 1, 6–14, January 2008, 18172517, 2171144, 10.1172/JCI32483, 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.JOURNAL, Romeo R, Knapp M, Tyrer P, Crawford M, Oliver-Africano P, The treatment of challenging behaviour in intellectual disabilities: cost-effectiveness analysis, Journal of Intellectual Disability Research, 53, 7, 633–43, July 2009, 19460067, 10.1111/j.1365-2788.2009.01180.x, Antipsychotics may be an option, together with stimulants, in people with ADHD and aggressive behavior when other treatments have not worked.JOURNAL, Linton, D, Barr, AM, Honer, WG, Procyshyn, RM, Antipsychotic and psychostimulant drug combination therapy in attention deficit/hyperactivity and disruptive behavior disorders: a systematic review of efficacy and tolerability., Current Psychiatry Reports, May 2013, 15, 5, 355, 10.1007/s11920-013-0355-6, 23539465, They have not been found to be useful for the prevention of delirium among those admitted to hospital.JOURNAL, Oh, ES, Needham, DM, Nikooie, R, Wilson, LM, Zhang, A, Robinson, KA, Neufeld, KJ, Antipsychotics for Preventing Delirium in Hospitalized Adults: A Systematic Review., Annals of internal medicine, 3 September 2019, 10.7326/M19-1859, 31476766,

Typicals versus atypicals

It is unclear whether the atypical (second-generation) antipsychotics offer advantages over older, first generation antipsychotics.JOURNAL, Kane JM, Correll CU, Pharmacologic treatment of schizophrenia, Dialogues in Clinical Neuroscience, 12, 3, 345–57, 2010, 20954430, 3085113, Amisulpride, olanzapine, risperidone and clozapine may be more effective but are associated with greater side effects.JOURNAL, Barry SJ, Gaughan TM, Hunter R, Schizophrenia, BMJ Clinical Evidence, 2012, June 2012, 23870705, 3385413,weblink dead,weblink" title="archive.is/20140911114812weblink">weblink 2014-09-11, Typical antipsychotics have equal drop-out and symptom relapse rates to atypicals when used at low to moderate dosages.JOURNAL, Schultz SH, North SW, Shields CG, Schizophrenia: a review, American Family Physician, 75, 12, 1821–9, June 2007, 17619525, Clozapine is an effective treatment for those who respond poorly to other drugs ("treatment-resistant" or "refractory" schizophrenia),JOURNAL, Taylor DM, Duncan-McConnell D, Refractory schizophrenia and atypical antipsychotics, Journal of Psychopharmacology, 14, 4, 409–18, 2000, 11198061, 10.1177/026988110001400411, but it has the potentially serious side effect of agranulocytosis (lowered white blood cell count) in less than 4% of people.JOURNAL, Essali A, Al-Haj Haasan N, Li C, Rathbone J, Clozapine versus typical neuroleptic medication for schizophrenia, The Cochrane Database of Systematic Reviews, 1, CD000059, January 2009, 19160174, 10.1002/14651858.CD000059.pub2, Due to bias in the research the accuracy of comparisons of atypical antipsychotics is a concern.JOURNAL, Heres S, Davis J, Maino K, Jetzinger E, Kissling W, Leucht S, Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics, The American Journal of Psychiatry, 163, 2, 185–94, February 2006, 16449469, 10.1176/appi.ajp.163.2.185, In 2005, a US government body, the National Institute of Mental Health published the results of a major independent study (the CATIE project).JOURNAL, Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK, Effectiveness of antipsychotic drugs in patients with chronic schizophrenia, The New England Journal of Medicine, 353, 12, 1209–23, September 2005, 16172203, 10.1056/NEJMoa051688, 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 typical antipsychotic perphenazine, although more patients discontinued perphenazine owing to extrapyramidal effects compared to the atypical agents (8% vs. 2% to 4%).JOURNAL, Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM, Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis, Lancet, 373, 9657, 31–41, January 2009, 19058842, 10.1016/S0140-6736(08)61764-X, Compliance has not been shown to be different between the two types.JOURNAL, Voruganti LP, Baker LK, Awad AG, New generation antipsychotic drugs and compliance behaviour, Current Opinion in Psychiatry, 21, 2, 133–9, March 2008, 18332660, 10.1097/YCO.0b013e3282f52851, Many researchers question the first-line prescribing of atypicals over typicals, and some even question the distinction between the two classes.JOURNAL, Paczynski RP, Alexander GC, Chinchilli VM, Kruszewski SP, Quality of evidence in drug compendia supporting off-label use of typical and atypical antipsychotic medications, The International Journal of Risk & Safety in Medicine, 24, 3, 137–46, January 2012, 22936056, 10.3233/JRS-2012-0567, JOURNAL, Owens, D. C., How CATIE brought us back to Kansas: a critical re-evaluation of the concept of atypical antipsychotics and their place in the treatment of schizophrenia, Advances in Psychiatric Treatment, 14, 1, 17–28, 2008, 10.1192/apt.bp.107.003970, JOURNAL, Fischer-Barnicol D, Lanquillon S, Haen E, Zofel P, Koch HJ, Dose M, Klein HE, Typical and atypical antipsychotics--the misleading dichotomy. Results from the Working Group 'Drugs in Psychiatry' (AGATE), Neuropsychobiology, 57, 1–2, 80–7, 2008, 18515977, 10.1159/000135641, 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.JOURNAL, Casey DE, Tardive dyskinesia and atypical antipsychotic drugs, Schizophrenia Research, 35, Suppl 1, S61–6, March 1999, 10190226, 10.1016/S0920-9964(98)00160-1, 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.JOURNAL, Makhinson M, Biases in medication prescribing: the case of second-generation antipsychotics, Journal of Psychiatric Practice, 16, 1, 15–21, January 2010, 20098227, 10.1097/01.pra.0000367774.11260.e4,

Adverse effects

{{for|more detailed comparison of atypical antipsychotics|Atypical antipsychotic#Adverse effects}}Biperiden is prescribed for acute extrapyramidal side effects of antypsychotic therapy, such as akathisiaweblink Information for professionals about Biperiden at www.drugs.comGenerally, more than one antipsychotic drug should not be used at a time because of increased adverse effects.{{Citation|title=Five Things Physicians and Patients Should Question|date=September 2013|url=http://www.choosingwisely.org/doctor-patient-lists/american-psychiatric-association/|author1=American Psychiatric Association|author1-link=American Psychiatric Association|work=Choosing Wisely: an initiative of the ABIM Foundation|page=|publisher=American Psychiatric Association|accessdate=30 December 2013|url-status = live|archiveurl=https://web.archive.org/web/20131203174206weblink|archivedate=3 December 2013|df=dmy-all}}, which cites
  • BOOK, 2006, Practice Guideline for the Treatment of Patients With Schizophrenia Second Edition, 1, 10.1176/appi.books.9780890423363.45859, 978-0-89042-336-3, Association, American Psychiatric,
  • {{Citation|title=Specifications Manual for Joint Commission National Quality Core Measures|date=30 June 2013|url=http://www.jointcommission.org/specifications_manual_joint_commission_national_quality_core_measures.aspx|author=Joint Commission|authorlink=Joint Commission|chapter=HBIPS-4, Patients discharged on multiple antipsychotic medications|chapter-url=http://manual.jointcommission.org/releases/TJC2013A/MIF0119.html|accessdate=27 October 2013|url-status = live|archiveurl=https://web.archive.org/web/20131110024015weblink|archivedate=10 November 2013|df=dmy-all}}
  • JOURNAL, Stahl SM, Grady MM, A critical review of atypical antipsychotic utilization: comparing monotherapy with polypharmacy and augmentation, Current Medicinal Chemistry, 11, 3, 313–27, February 2004, 14965234, 10.2174/0929867043456070,
Very rarely antipsychotics may cause tardive psychosis.BOOK, Moore, David P., Puri, Basant K., vanc, Textbook of Clinical Neuropsychiatry and Behavioral Neuroscience, Third Edition, 2012, CRC Press, 9781444164947, 791,weblink en, live,weblink 25 November 2017, dmy-all,

By rate

Common (≥ 1% and up to 50% incidence for most antipsychotic drugs) adverse effects of antipsychotics include:JOURNAL, Muench J, Hamer AM, Adverse effects of antipsychotic medications, American Family Physician, 81, 5, 617–22, March 2010, 20187598,
  • Sedation (particularly common with asenapine, clozapine, olanzapine, quetiapine, chlorpromazine and zotepine)
  • Headaches
  • Dizziness
  • Diarrhea
  • Anxiety
  • Extrapyramidal side effects (particularly common with first-generation antipsychotics), which include:


- Akathisia — an often distressing sense of inner restlessness. - Dystonia - Parkinsonism - Tremor
  • Hyperprolactinaemia (rare for those treated with clozapine, quetiapine and aripiprazole), which can cause:


- Galactorrhoea — unusual secretion of breast milk. - Gynaecomastia - Sexual dysfunction (in both sexes) - Osteoporosis
  • Orthostatic hypotension
  • Weight gain (particularly prominent with clozapine, olanzapine, quetiapine and zotepine)
  • Anticholinergic side-effects (common for olanzapine, clozapine; less likely on risperidoneJOURNAL, Lieberman JA, Managing anticholinergic side effects, Primary Care Companion to the Journal of Clinical Psychiatry, 6, Suppl 2, 20–3, 2004, 16001097, 487008, ) such as:


- Blurred vision - Constipation - Dry mouth (although hypersalivation may also occur) - Reduced perspiration
  • Tardive dyskinesia appears to be more frequent with high-potency first-generation antipsychotics, such as haloperidol, and tends to appear after chronic and not acute treatment.BOOK, Stahl SM, Stahl's Essential Psychopharmacology: Neuroscientific basis and practical applications,weblink registration, Cambridge University Press, 2008, {{page needed|date=July 2013}} It is characterized by slow (hence the tardive) repetitive, involuntary and purposeless movements, most often of the face, lips, legs, or torso, which tend to resist treatment and are frequently irreversible. The rate of appearance of TD is about 5% per year of use of antipsychotic drug (whatever the drug used).


Rare/Uncommon (


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