Antipsychotics discontinuation

Treatment should begin with antipsychotic discontinuation and supportive care. 

Since early detection and intervention in schizophrenia is important for maximizing outcomes, treatment with antipsychotic medications should begin as soon as psychotic symptoms are recognized. Antipsychotic medications are the cornerstone of therapy for people with schizophrenia, and most patients are on lifelong therapy since non-adherence and discontinuation of antipsychotics are associated with high relapse rates. If other symptoms are present such as depression and anxiety, these symptoms should also be aggressively treated. Additionally, psychosocial treatments should be used concomitantly to improve patient outcomes. 

Essentially all antipsychotic medications pass through the placenta. The use of these drugs requires critical attention to the timing of the exposure, the dose and duration of use, and fetal susceptibility. When possible, discontinuing antipsychotics for the first trimester is the safest option, as weeks 6 to 10 are the most vulnerable period for organ formation. 

Stroup, T. S., Lieberman, J. A., McEvoy, J. P. et al. (2006). Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am. J. Psychiatry, 163, 611-22. 

Higher initial doses of antipsychotics (e.g., 20 mg/day of olanzapine) are required for acute mania, but once mania is controlled (usually 7 to 28 days), the antipsychotic can be gradually tapered and discontinued, and the patient maintained on the mood stabilizer alone. 

Combining lithium with typical antipsychotics may cause neurotoxicity (e.g., delirium, cerebellar dysfunction, extrapyramidal symptoms). Lithium should be withdrawn and discontinued at least 2 days before electroconvulsive therapy. 

Antipsychotics (especially FGAs and clozapine) should be tapered slowly before discontinuation to avoid rebound cholinergic withdrawal symptoms. 

In general, when switching from one antipsychotic to another, the first should be tapered and discontinued over 1 to 2 weeks after the second antipsychotic is initiated. 

Combining an FGA and an SGA and combining different SGAs have been suggested, but no data exist to support or refute these strategies. If a series of antipsychotic monotherapies fails, a time-limited combination trial may be attempted. If there is no improvement within 6 to 12 weeks, one of the drugs should be tapered and discontinued. 

If the white blood cell (WBC) count is less than 3,000/mm3 or the absolute neutrophil count (ANC) is less than 1,000/mm3, the antipsychotic should be discontinued, and the WBC count monitored closely until it returns to normal. 

It is also very important, if possible, to discontinue or lower the doses of drugs with anticholinergic effects antihistamines, antipsychotics, antidepressants, uro-logic spasmolytics, anti-arrhythmics, drugs for Parkinson s disease and more. Prophylactic treatment against Candida infection, bacteria and caries can also be useful (Mouly et al. 2007). 

However, when there is clear evidence of persistent illness or when the patient endures several acute episodes of illness, treatment shonld be indefinite and probably lifelong. Except in the residual phases of illness, discontinuing antipsychotic medication exposes the schizophrenia patient to a serious risk of relapse. However, there is evidence that gradually decreasing the dose of antipsychotic in 4 week intervals can still provide good protection from relapse while lowering the risk of side effects. 

Tardive Dyskinesia (TD). As mentioned previously, TD is a potential side effect of long-term treatment with typical antipsychotics it is believed to be very rare but possible after atypical antipsychotic treatment. Although we now know that TD is not irreversible in all patients, about half will recover after discontinuation of the antipsychotic and the passage of several months time, others will exhibit the symp-... 

Seizures Bupropion is associated with a dose-related risk of seizures. Discontinue bupropion and do not restart in patients who experience a seizure while on treatment. Use extreme caution when bupropion is administered to patients with a history of seizure, cranial trauma, or other predisposition(s) toward seizure, or prescribed with other agents (eg, antipsychotics, other antidepressants, theophylline, systemic steroids) that lower seizure threshold. 

ECG changes - A minority of clozapine patients experience ECG repolarization changes similar to those seen with other antipsychotic drugs, including S-T segment depression and flattening or inversion of T waves, which all normalize after discontinuation of clozapine. 

Maintenance Evaluation of patients with schizophrenia who had been stable on other antipsychotic medications for periods of 3 months or longer, were discontinued from those medications, and were then administered aripiprazole 15 mg/day and who were observed for relapse for up to 26 weeks demonstrated a benefit of such maintenance treatment. Periodically reassess patients to determine the need for maintenance treatment. 

Switching from other antipsychotics - Nh e immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, gradual discontinuation may be more appropriate for others. In all cases, minimize the period of overlapping antipsychotic administration. 

The recommended dose is 25 mg IM every 2 weeks. Some patients not responding to 25 mg may benefit from a higher dose of 37.5 or 50 mg. The maximum dose should not exceed risperidone injection 50 mg every 2 weeks. Give oral risperidone or another antipsychotic medication with the first risperidone injection and continue for 3 weeks (then discontinue) to ensure that adequate therapeutic plasma concentrations are maintained prior to the main release phase of risperidone from the injection site. 

Concomitant medications - Many medications (eg, antipsychotics, antidepressants, theophylline, systemic steroids) and treatment regimens (eg, abrupt discontinuation of benzodiazepines) are known to lower seizure threshold. 

Two extrapyramidal conditions, acute dystonia and akathisia, occur early during treatment, while parkinsonism tends to evolve gradually over days to weeks. All three reactions occur most commonly with the high-potency antipsychotics (Table 34.1) and are related to high Dz-receptor occupancy. Acute dystonia, which occurs in about 5% of patients on antipsychotic therapy, consists of uncontrollable movements and distortions of the face, head, and neck. It can be treated with centrally acting an-timuscarinic agents, such as benztropine, while antipsychotic therapy is temporarily discontinued. When this reaction subsides, the anticholinergic can be withdrawn. 

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