Antipsychotics drug also known as neuroleptics or major tranquilizers, are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. They are increasingly being used in the management of non-psychotic disorders. Antipsychotics are usually effective in relieving symptoms of psychosis in the short term.

The long-term use of antipsychotics is associated with side effects such as involuntary movement disorders, gynecomastia, and metabolic syndrome. They are also associated with increased mortality in elderly people with dementia.

Classification of Antipsychotics Drug

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Generic name	Brand names	Chemical class	ATC code
typical antipsychotics
Acepromazine	Atravet, Acezine	phenothiazine	N05AA04
Acetophenazine	Tindal	phenothiazine	N05AB07
Benperidol	Frenactyl	butyrophenone	N05AD07
Bromperidol	Bromidol, Bromodol	butyrophenone	N05AD06
Butaperazine	Repoise, Tyrylen	phenothiazine	N05AB09
Carfenazine		phenothiazine
Chlorproethazine		phenothiazine	N05AA07
Chlorpromazine	Largactil, Thorazine	phenothiazine	N05AA01
Chlorprothixene	Cloxan, Taractan, Truxal	thioxanthene	N05AF03
Clopenthixol	Sordinol	thioxanthene	N05AF02
Cyamemazine	Tercian	phenothiazine	N05AA06
Dixyrazine	Esucos	phenothiazine	N05AB01
Droperidol	Droleptan, Dridol, Inapsine, Xomolix, Innovar (+ Fentanyl)	phenylbutylamine (butyrophenone)	N05AD08
Fluanisone		butyrophenone	N05AD09
Flupentixol	Depixol, Fluanxol	thioxanthene	N05AF01
Fluphenazine	Prolixin, Modecate	phenothiazine	N05AB02
Fluspirilene	Redeptin, Imap	diphenylbutylpiperidine	N05AG01
Haloperidol	Haldol	phenyl-piperidinyl-butyrophenone	N05AD01
Levomepromazine	Nosinan, Nozinan, Levoprome	phenothiazine	N05AA02
Lenperone	Elanone-V	butyrophenone
Loxapine	Loxapac, Loxitane	dibenzoxazepine	N05AH01
Mesoridazine	Serentil	phenothiazine	N05AC03
Metitepine		tricylic dibenzodiazepine
Molindone	Moban	indole derivative	N05AE02
Moperone	Luvatren	butyrophenone	N05AD04
Oxypertine	Equipertine, Forit, Integrin, Lanturil, Lotawin, Opertil	phenylpiperazine	N05AE01
Oxyprotepine	Moditen (Czech republic)	dibenzothiepine
Penfluridol	Semap, Micefal, Longoperidol	diphenylbutylpiperidine	N05AG03
Perazine	Taxilan	phenothiazine	N05AB10
Periciazine	Neuleptil, Neulactil	phenothiazine	N05AC01
Perphenazine	Trilafon	phenothiazine	N05AB03
Pimozide	Orap	diphenylbutylpiperidine	N05AG02
Pipamperone	Dipiperon, Dipiperal, Piperonil, Piperonyl, Propitan	butyrophenone	N05AD05
Piperacetazine	Quide	phenothiazine
Pipotiazine	Piportil	phenothiazine	N05AC04
Prochlorperazine	Compazine, Stemzine, Buccastem, Stemetil, Phenotil	phenothiazine	N05AB04
Promazine	Sparine	phenothiazine	N05AA03
Prothipendyl		phenothiazines	N05AX07
Spiperone	Spiroperidol, Spiropitan	butyrophenone
Sulforidazine	Imagotan, Psychoson, Inofal	phenothiazine
Thiopropazate	Artalan, Dartal, Dartalan, Dartan	phenothiazine	N05AB05
Thioproperazine	Majeptil	phenothiazine	N05AB08
Thioridazine	Mellaril, Melleril	phenothiazine	N05AC02
Thiothixene	Navane	thioxanthene	N05AF04
Timiperone		butyrophenone
Trifluoperazine	Stelazine	phenothiazine	N05AB06
Trifluperidol		butyrophenone	N05AD02
Triflupromazine	Vesprin	phenothiazine	N05AA05
Zuclopenthixol	Clopixol	thioxanthene	N05AF05
atypical antipsychotics
Amoxapine	Asendin, Asendis, Defanyl, Demolox	dibenzoxazepine	N06AA17
Amisulpride	Amazeo, Amipride, Amival, Solian, Soltus, Sulpitac, Sulprix	substituted benzamides	N05AL05
Aripiprazole	Abilify	quinolone	N05AX12
Asenapine	Saphris	dibenzo-oxepino pyrrole	N05AH05
Blonanserin	Lonasen
Brexpiprazole	Rexulti	quinolone	N05AX16
Cariprazine	Vraylar		N05AX15
Carpipramine	Prazinil, Defekton
Clocapramine	Clofekton, Padrasen	imidobenzyl
Clorotepine	Clotepin, Clopiben	tricylic dibenzodiazepine
Clotiapine	Entumine		N05AH06
Clozapine	Clozaril	tricylic dibenzodiazepine	N05AH02
Iloperidone	Fanapt	benzisoxazole	N05AX14
Levosulpiride		benzamide	N05AL07
Lurasidone	Latuda	n-arylpiperazine (piperazine)	N05AE05
Melperone	Bunil, Buronil, Eunerpan	butyrophenone	N05AD03
Mosapramine	Cremin		N05AX10
Nemonapride	Emilace	benzamide
Olanzapine	Zyprexa, Ozace, Lanzek, Zypadhera	thienobenzodiazepine	N05AH03
Paliperidone	Invega	pyridopyrimidine	N05AX13
Perospirone	Lullan	azapirone
Quetiapine	Seroquel	dibenzothiazepine	N05AH04
Remoxipride	Roxiam	salicylamide	N05AL04
Reserpine	Raudixin, Serpalan, Serpasil	yohimbine alkaloid	C02AA02
Risperidone	Risperdal, Zepidone	pyridopyrimidine	N05AX08
Sertindole	Serdolect	phenylpyrrole	N05AE03
Sulpiride	Sulpirid, Eglonyl	benzenesulfonamide (benzamide)	N05AL01
Sultopride	Barnetil, Barnotil, Topral	benzamide	N05AL02
Tiapride	Equilium, Tiapridal	benzamide	N05AL03
Veralipride	Agreal, Agradil	benzamide	N05AL06
Ziprasidone	Geodon, Zeldox	n-arylpiperazine (piperazine)	N05AE04
Zotepine	Nipolept	tricylic dibenzodiazepine	N05AX11
under development
perphenazine gamma-aminobutyrate	BL-1020
Pimavanserin	ACP-103
	F-15063
	ITI-007	tetracyclic quinoxaline
	Lu AF35700
	RP5063
Stepholidine		berberine
development abandoned
Amperozide		diphenylbutylpiperazine	QN05AX90
Bifeprunox	DU-127,090	biphenyl derivative
Butaclamol	AY-23,028
Ciclindole	WIN-27,147-2
Clopimozide	R-29,764	diphenylbutylpiperidine
Elopiprazole	DU-29894	phenylpiperazine
Flucindole
Fluotracen	SKF-28,175
Fluperlapine	NB 106-689	tricyclic
Gevotroline	WY-47,384	tricylic dibenzodiazepine
Naranol	W-5494A
N-desmethylclozapine	ACP-104
Ocaperidone	R 79598	benzisoxazole
Piquindone	Ro 22-1319	tricyclic
Pomaglumetad	LY2140023
Tiospirone	BMY-13,859	azapirone
Umespirone	KC-9172	azapirone
Vabicaserin	SCA-136
Volinanserin	MDL-100,907
Zetidoline	DL 308-IT
Zicronapine	Lu 31-130

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First-generation (typical)

Butyrophenones

• Benperidol
• Bromperidol
• Droperidol
• Haloperidol
• Moperone
• Pipamperone
• Timiperone

Diphenylbutylpiperidines

• Fluspirilene
• Penfluridol
• Pimozide

Phenothiazines

• Acepromazine — although it is mostly used in veterinary medicine.
• Chlorpromazine
• Cyamemazine
• Dixyrazine
• Fluphenazine
• Levomepromazine
• Mesoridazine
• Perazine
• Pericyazine
• Perphenazine
• Pipotiazine
• Prochlorperazine
• Promazine (discontinued))
• Promethazine
• Prothipendyl
• Thioproperazine(only English-speaking country it is available in is Canada)
• Thioridazine (discontinued)
• Trifluoperazine
• Triflupromazine (discontinued))^†

Thioxanthenes

• Chlorprothixene
• Clopenthixol
• Flupentixol
• Thiothixene
• Zuclopenthixol

Disputed/unknown

This category is for drugs that have been called both first and second-generation, depending on the literature being used.

Benzamides

• Sulpiride
• Sultopride
• Veralipride

Tricyclics

• Carpipramine
• Clocapramine
• Clorotepine
• Clotiapine
• Loxapine
• Mosapramine

Others

• Molindone

Second-generation (atypical)

Benzamides

• Amisulpride  Selective dopamine antagonist. Higher doses (greater than 400 mg) act upon post-synaptic dopamine receptors resulting in a reduction in the positive symptoms of schizophrenia, such as psychosis. Lower doses, however, act upon dopamine autoreceptors, resulting in increased dopamine transmission, improving the negative symptoms of schizophrenia. Lower doses of amisulpride have also been shown to have antidepressant and anxiolytic effects in non-schizophrenic patients, leading to its use in dysthymia and social phobias.
• Nemonapride – Used in Japan.
• Remoxipride – Has a risk of causing aplastic anemia and, hence, has been withdrawn from the market worldwide. It has also been found to possess relatively low (virtually absent) potential to induce hyperprolactinemia and extrapyramidal symptoms, likely attributable to its comparatively weak binding to (and, hence, rapid dissociation from) the D₂ receptor.
• Sultopride – An atypical antipsychotic of the benzamide chemical class used in Europe, Japan, and Hong Kong for the treatment of schizophrenia. It was launched by Sanofi-Aventis in 1976. Sultopride acts as a selective D2 and D3 receptor antagonist.

Benzisoxazoles/benzisothiazoles

• Iloperidone – Approved by the US FDA in 2009, it is fairly well tolerated, although hypotension, dizziness, and somnolence were very common side effects. Has not received regulatory approval in other countries, however.
• Lurasidone – Approved by the US FDA for schizophrenia and bipolar depression. Given once daily, it has shown mixed Phase III efficacy results but has a relatively well-tolerated side effect profile. It is also licensed for use as schizophrenia treatment in Canada. Not yet licensed elsewhere, however. Has procognitive effects via its antagonism of the 5-HT₇ receptor.
• Paliperidone – Primary Metabolite of risperidone that was approved in 2006.
• Paliperidone palmitate – Long-acting version of paliperidone for once-monthly injection.
• Perospirone ^† – Has a higher incidence of extrapyramidal side effects than other atypical antipsychotics.
• Risperidone – Divided dosing is recommended until initial titration is completed, at which time the drug can be administered once daily. Used off-label to treat Tourette syndrome and anxiety disorder.
• Ziprasidone – Approved in 2004 to treat bipolar disorder. Side-effects include a prolonged QT interval in the heart, which can be dangerous for patients with heart disease or those taking other drugs that prolong the QT interval.

Butyrophenones

• Melperone – Only used in a few European countries. No English-speaking country has licensed it to date.

Phenylpiperazines/quinolinones

• Aripiprazole – partial agonist at the D₂ receptor, unlike almost all other clinically-utilized antipsychotics.
• Aripiprazole lauroxil – Long-acting version of aripiprazole for injection.
• Brexpiprazole – Partial agonist of the D₂ receptor. The successor of aripiprazole.
• Cariprazine – A D₃-preferring D₂/D₃ partial agonist.

Tricyclics

• Asenapine – Used for the treatment of schizophrenia and acute mania associated with bipolar disorder.
• Clozapine – Requires complete blood counts every one to four weeks due to the risk of agranulocytosis. It has unparalleled efficacy in the treatment of treatment-resistant schizophrenia.
• Olanzapine – Used to treat psychotic disorders including schizophrenia, acute manic episodes, and maintenance of the bipolar disorder. Used as an adjunct to antidepressant therapy, especially to fluoxetine treatment in the form of Symbyax.
• Quetiapine – Used primarily to treat bipolar disorder and schizophrenia. Also used and licensed in a few countries (including Australia, the United Kingdom, and the United States) as an adjunct to antidepressant therapy in patients with major depressive disorder. It’s the only antipsychotic that’s demonstrated efficacy as a monotherapy for the treatment of the major depressive disorder. It indirectly serves as a norepinephrine reuptake inhibitor by means of its active metabolite, no quetiapine.
• Zotepine – An atypical antipsychotic indicated for acute and chronic schizophrenia. It is still used in Japan and was once used in Germany but it was discontinued.^†

Others

• Blonanserin – Approved by the PMDA in 2008. Used in Japan and South Korea.
• Pimavanserin – A selective 5-HT_2A receptor antagonist approved for the treatment of Parkinson’s disease psychosis in 2016.
• Sertindole ^‡ – Developed by the Danish pharmaceutical company H. Lundbeck. Like the other atypical antipsychotics, it is believed to have antagonist activity at dopamine and serotonin receptors in the brain.

Mechanism of Action of Antipsychotics Drug

Antipsychotic drugs such as haloperidol and chlorpromazine tend to block dopamine D₂ receptors in the dopaminergic pathways of the brain. This means that dopamine released in these pathways has less effect. Excess release of dopamine in the mesolimbic pathway has been linked to psychotic experiences. Decreased dopamine release in the prefrontal cortex and excess dopamine release in another pathway are associated with psychotic episodes in schizophrenia and bipolar disorder. In addition to the antagonistic effects of dopamine, antipsychotics (in particular atypical neuroleptics) also antagonize 5-HT_2A receptors. Different alleles of the 5-HT_2A receptor have been associated with schizophrenia and other psychoses, including depression. Higher concentrations of 5-HT_2A receptors in cortical and subcortical areas, in particular in the right caudate nucleus have been historically recorded. This is the same receptor that psychedelic drugs agonize to various degrees, which explains the correlation between psychedelic drugs and schizophrenia.

Typical antipsychotics are not particularly selective and also block dopamine receptors in the mesocortical pathway, tuberoinfundibular pathway, and the nigrostriatal pathway. Blocking D₂ receptors in these other pathways is thought to produce some.

Atypical antipsychotic drugs have a similar blocking effect on D₂ receptors, however, most also act on serotonin receptors, especially 5-HT_2A and 5-HT_2C receptors. Both clozapine and quetiapine appear to bind just long enough to elicit antipsychotic effects but not long enough to induce extrapyramidal side effects and prolactin hypersecretion.5-HT_2A antagonism increases dopaminergic activity in the nigrostriatal pathway, leading to a lowered extrapyramidal side effect liability among the atypical antipsychotics

Indications of Antipsychotics Drug

• Schizophrenia
• The schizoaffective disorder most commonly in conjunction with either an antidepressant (in the case of the depressive subtype) or a mood stabilizer (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 favorable adverse effect profiles and, according to a recent meta-analysis, they tend to have a lower liability for causing the conversion from mania to depression.
• 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

Contra-Indications of Antipsychotics Drug

• The high amount of ammonium in the blood
• Porphyria
• Having thoughts of suicide
• Alcohol Intoxication
• drug abuse
• Depression
• Unconsciousness resulting from liver cell deterioration
• Severe liver disease
• Temporarily stops breathing while sleeping
• Pregnancy
• Poisoning by drug

Side Effects of Antipsychotics Drug

The most common

• Memory or concentration problems
• Excitement, irritability, aggression, or confusion
• Dizziness
• constipation
• muscle aches
• Nausea and vomiting
• Severe stomach ache
• diarrhea,
• anorexia,
• flatulence,
• headache,
• dizziness,
• heartburn
• joint pain

 Common

• Memory loss.
• Impaired attention span.
• Agitation.
• Depression.
• Nausea and vomiting
• Severe stomach ache
• Severe diarrhea
• Mouth sores
• Vaginal thrush
• Skin rash
• Headache

Rare/Less common

• Confusion
• Fever or sore throat
• Rash
• Slowed breathing or breathing difficulties
• Sores in the mouth
• Broken blood vessels under the skin
• Easy bruising or bleeding
• Swelling of the eyes, lips, or cheeks
• Blistering or peeling of the skin
• Restless muscle movements in the eyes, tongue, jaw, or neck

Drug Interactions of Antipsychotics Drug

Antipsychotic drugs may interact with the following drugs, supplements & may change the efficacy of drugs

• albendazole
• alcohol
• allopurinol
• antihistamines (e.g,. cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
• antiseizure medications e.g., clobazam, levetiracetam, phenobarbital, phenytoin, valproic acid, zonisamide)
• aripiprazole
• “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
• benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
• beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
• calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
• captopril
• celecoxib
• chloroquine
• cholecalciferol
• cyclosporine
• dantrolene
• domperidone
• “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
• gabapentin
• H2 antagonists (e.g., famotidine, ranitidine)
• mirabegron
• montelukast
• non-steroidal anti-inflammatory medications (NSAIDs;e.g., diclofenac, ibuprofen, serotonin antagonists (anti-emetic medications;, naproxen)
• phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
• quinolone antibiotics (e.g., levofloxacin, norfloxacin, moxifloxacin)
• selective serotonin reuptake inhibitors (SSRIs; e.g., paroxetine, fluoxetine, citalopram) e.g., granisetron, ondansetron)
• “statin” anti-cholesterol medications (e.g., atorvastatin, lovastatin, simvastatin)
• theophylline
• thiazide diuretics (water pills; e.g., hydrochlorothiazide, indapamide, metolazone)
• tramadol
• tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine,
• selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
• sildenafil
• tramadol
• tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
• valproic acid
• warfarin
• zafirlukast

References

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