At a glance......
- 1 Classification of Antipsychotics Drug
- 2 First-generation (typical)
- 3 Second-generation (atypical)
- 4 Mechanism of Action of Antipsychotics Drug
- 5 Indications of Antipsychotics Drug
- 6 Contra-Indications of Antipsychotics Drug
- 7 Side Effects of Antipsychotics Drug
- 8 Drug Interactions of Antipsychotics Drug
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
- Acepromazine — although it is mostly used in veterinary medicine.
- Promazine (discontinued))
- Thioproperazine(only English-speaking country it is available in is Canada)
- Thioridazine (discontinued)
- Triflupromazine (discontinued))†
This category is for drugs that have been called both first and second-generation, depending on the literature being used.
- 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- Remoxipride – Has a risk of causing aplastic anemia and, hence, has been withdrawn from the market worldwide.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.
- 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.
- Melperone – Only used in a few European countries. No English-speaking country has licensed it to date.
- 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.
- 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.†
- Blonanserin – Approved by the PMDA in 2008. Used in Japan and South Korea.
- Pimavanserin – A selective 5-HT2A 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-HT2A receptors. Different alleles of the 5-HT2A receptor have been associated with schizophrenia and other psychoses, including depression. Higher concentrations of 5-HT2A 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-HT2A and 5-HT2C 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-HT2A antagonism increases dopaminergic activity in the nigrostriatal pathway, leading to a lowered extrapyramidal side effect liability among the atypical antipsychotics
Indications of Antipsychotics Drug
- 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
- Having thoughts of suicide
- Alcohol Intoxication
- drug abuse
- Unconsciousness resulting from liver cell deterioration
- Severe liver disease
- Temporarily stops breathing while sleeping
- Poisoning by drug
Side Effects of Antipsychotics Drug
The most common
- Memory or concentration problems
- Excitement, irritability, aggression, or confusion
- muscle aches
- Nausea and vomiting
- Severe stomach ache
- joint pain
- Memory loss.
- Impaired attention span.
- Nausea and vomiting
- Severe stomach ache
- Severe diarrhea
- Mouth sores
- Vaginal thrush
- Skin rash
- Fever or sore throat
- 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
- antihistamines (e.g,. cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- antiseizure medications e.g., clobazam, levetiracetam, phenobarbital, phenytoin, valproic acid, zonisamide)
- “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)
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- H2 antagonists (e.g., famotidine, ranitidine)
- 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)
- thiazide diuretics (water pills; e.g., hydrochlorothiazide, indapamide, metolazone)
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine,
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
- valproic acid