There appears to be a dose-dependent risk for seizures with<unk>  treatment. Tardive dyskinesia (involuntary, repetitive body movements) and akathisia (a feeling of inner restlessness and inability to stay still) are less commonly seen with<unk>  than they are with high potency typical antipsychotics such as haloperidol or trifluoperazine, and some evidence suggests that, with conservative dosing, the incidence of such effects for<unk>  may be comparable to that of newer agents such as risperidone or olanzapine.<unk>  may deposit in ocular tissues when taken in high dosages for long periods of time. + Comparison of<unk>  to placebo Measured outcome Findings summary Findings range Quality of evidence Adverse effects Weight gain 5 times more likely to have considerable weight gain, around 40% with<unk>  gaining weight RR 4.9 CI 2.3 to 10.4 Very low (estimate of effect uncertain) Sedation 3 times more likely to cause sedation, around 30% with<unk>  RR 2.8 CI 2.3 to 3.5 Acute movement disorder 3.5 times more likely to cause easily reversible but unpleasant severe stiffening of muscles, around 6% with<unk>  RR 3.5 CI 1.5 to 8.0 Parkinsonism 2 times more likely to cause parkinsonism (symptoms such as tremor, hesitancy of movement, decreased facial expression), around 17% with<unk>  RR 2.1 CI 1.6 to 2.8 Decreased blood pressure with dizziness 3 times more likely to cause decreased blood pressure and dizziness, around 15% with<unk>  RR 2.4 CI 1.7 to 3.3 Contraindications Absolute contraindications include: * Circulatory depression * CNS depression * Coma * Drug intoxication * Bone marrow suppression * Phaeochromocytoma * Hepatic failure * Active liver disease * Previous hypersensitivity (including jaundice, agranulocytosis, etc.) to phenothiazines, especially<unk> , or any of the excipients in the formulation being used. Relative contraindications include: * Epilepsy * Parkinson's disease * Myasthenia gravis * Hypoparathyroidism * Prostatic hypertrophy Very rarely, elongation of the QT interval may occur, increasing the risk of potentially fatal arrhythmias. Interactions Consuming food prior to taking<unk>  orally limits its absorption; likewise, cotreatment with benztropine can also reduce<unk>  absorption. Alcohol can also reduce<unk>  absorption. Antacids slow<unk>  absorption. Lithium and chronic treatment with barbiturates can increase<unk>  clearance significantly. Tricyclic antidepressants (TCAs) can decrease<unk>  clearance and hence increase<unk>  exposure. Cotreatment with CYP1A2 inhibitors like ciprofloxacin, fluvoxamine or vemurafenib can reduce<unk>  clearance and hence increase exposure and potentially also adverse effects.<unk>  can also potentiate the CNS depressant effects of drugs like barbiturates, benzodiazepines, opioids, lithium and anesthetics and hence increase the potential for adverse effects such as respiratory depression and sedation. Chlorprozamine is also a moderate inhibitor of CYP2D6 and a substrate for CYP2D6, and hence can inhibit its own metabolism. It can also inhibit the clearance of CYP2D6 substrates such as dextromethorphan, potentiating their effects. Other drugs like codeine and tamoxifen, which require CYP2D6-mediated activation into their respective active metabolites, may have their therapeutic effects attenuated. Likewise, CYP2D6 inhibitors such as paroxetine or fluoxetine can reduce<unk>  clearance, increasing serum levels of<unk>  and potentially its adverse effects.<unk>  also reduces phenytoin levels and increases valproic acid levels. It also reduces propranolol clearance and antagonizes the therapeutic effects of antidiabetic agents, levodopa (a Parkinson's medication. This is likely due to the fact that<unk>  antagonizes the D2 receptor which is one of the receptors dopamine, a levodopa metabolite, activates), amphetamines and anticoagulants. It may also interact with anticholinergic drugs such as orphenadrine to produce hypoglycaemia (low blood sugar).<unk>  may also interact with epinephrine (adrenaline) to produce a paradoxical fall in blood pressure. Monoamine oxidase inhibitors (MAOIs) and thiazide diuretics may also accentuate the orthostatic hypotension experienced by those receiving<unk>  treatment. Quinidine may interact with<unk>  to increase myocardial depression. Likewise, it may also antagonize the effects of clonidine and guanethidine. It also may reduce the seizure threshold and hence a corresponding titration of anticonvulsant treatments should be considered. Prochlorperazine and desferrioxamine may also interact with<unk>  to produce transient metabolic encephalopathy. Other drugs that prolong the QT interval, such as quinidine, verapamil, amiodarone, sotalol and methadone, may also interact with<unk>  to produce additive QT interval prolongation. Discontinuation The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly, there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time. There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely, tardive dyskinesia can occur when the medication is stopped.
Chlorpromazine
Chlortalidone
Clozapine
Desmethylclozapine
Haloperidol
Thioridazine
Trimipramine
Primidone