Ans. c (Olanzapine) (Ref: Harrison's internal medicine, 16th ed., p 2418)ATYPICAL ANTIPSYCHOTICS (Noval antipsychotics like)# Atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) significantly lower the risk of tardive dyskinesia (TD) compared to typical antipsychotics.- Clozapine,- Quetiapine, - Ziprasidone,- Olanzapine,- Risperidone,- Aripiprazole.(Mnemonic: C Q ZORA)# Risperidone, a benzisoxazole derivative, is more potent at 5HT2 than D2 receptor sites, like clozapine, but it also exerts significant alpha-2 antagonism, a property that may contribute to its perceived ability to improve mood and increase motor activity. Risperidone is not as effective as clozapine in treatment-resistant cases but does not carry a risk of blood dyscrasias.# Olanzapine is similar neurochemically to clozapine but has a significant risk of inducing weight gain.# Quetiapine is distinct in having a weak D2 effect but potent alpha-1 and histamine blockade.# Ziprasidone causes minimal weight gain and is unlikely to increase prolactin, but may increase QT prolongation.# Aripiprazole also has little risk of weight gain or prolactin increase but may increase anxiety, nausea, and insomnia as a result of its partial agonist properties.Extrapyramidal side effectsEarly onset and reversibleDystoniaInvoluntary contraction primarily of the face, neck, tongue and extraocular musclesResponds to anticholinergicsParkinsonAkinesia, muscle rigidity, tremor, shuffling gait (typically appearing in that order)AkathisiaMotor restlessness and the urge to moveLate onset and IrreversibleTardive dyskinesis (TD)# Diagnosis requires exposure to neuroleptics for at least 3 months, but often take longer # Involuntary repetitive movements of lips, face, tongue, limbs# Try to prevent by using lowest possible dose of antipsychotic medication# Anticholinergics worsen TD# Try to reduce dose or discontinue medication if TD occurs (although increasing dose will temporarily mask symptoms)# Switch to an atypical antipsychoticAtypical AntipsychoticsDrugsCharacteristicsSide effectsClozapineRisperidoneOlanzapineQuetipineZiprasidineAripiprazole# Generally good 5HT2 antagonists and weaker D2 antagonists# Treats positive and negative symptoms of schizophrenia (typicals treat mostly positive)# Less EPS# Tend to be more expensive than typicals# Clozapine: agranulocytosis# Ziprasidone: prolongs QT interval, may lead to torsadede pointes# Risperidone: some EPSEducational points:Tardive dyskinesia# Occurs primarily due to chronic exposure to central dopamine blockers.# Rx:- Approximately one-third of patients with TD remit within 3 months of stopping neuroleptic therapy, and in most patients the movements will gradually remit within 5 years.- Abrupt drug cessation may result in "withdrawal dyskinesias," i.e. frank TD.- In refractory cases, choreatic TD catecholamine depletors reserpine and tetrabenazine are useful.- Another strategy employ is GABAergic medications such as baclofen (40 to 80 mg/d), clonazepam (1 to 8 mg/d), or valproic acid (750 to 3,000 mg/d), which are particularly helpful in patients with tardive dystonia, which may also benefit from anticholinergic therapy and botulinum toxin injections.