125 - Withdrawal effects of antipsychotics

Withdrawal effects of antipsychotics

Schizophrenia and related psychoses CHAPTER 1 Stopping antipsychotics Antipsychotics are recommended for long-­term treatment of schizophrenia because they reduce symptoms and lessen the risk of relapse.1 However, antipsychotics have many adverse effects, including metabolic complications, TD, emotional blunting and anatomical brain changes.2 There is some (hotly disputed) evidence that reducing or stopping antipsychotics may improve social functioning (relationships, education or employment, independent living) without worsening the rate of relapse or symptom burden in the medium term,3 although it might increase risk of relapse in the short term.4,5 Reducing antipsychotic burden may also improve cognitive functioning.6 It is also worth considering that much of the evidence for the relapse prevention properties of antipsychotics relies on discontinuation trials in which antipsychotics are stopped quickly (over a matter of weeks), and that process may have elevated the apparent rate of relapse in the discontinuation group, so exaggerating the relapse prevention properties of antipsychotics.7 Patients often ask to reduce or stop medication and, in light of the above, this may be a reasonable course of action. Cautious deprescribing should be a component of high-­quality prescribing practice, depending on the condition being treated. More than half of antipsychotic prescriptions in the UK are given to patients without a psychotic or manic disorder and instead are prescribed for insomnia, anxiety, personality disorders and symptoms of dementia.8 In the UK, NICE strongly cautions against medium- or long-­term use of antipsychotics in personality disorder,9 and only limited use in dementia.10 The principles for deprescribing outlined below also apply to these patients. Withdrawal effects of antipsychotics Stopping or reducing the dose of an antipsychotic can cause a variety of withdrawal symptoms reflecting their various actions (blocking dopamine, histamine, acetylcholine, serotonin and noradrenaline receptors).11,12 Symptoms are listed in Figure 1.2.11–15 Importantly, withdrawal/discontinuation symptoms from antipsychotics can include psychotic symptoms.12,16 This is suggested by a number of case studies in which people without a psychotic disorder treated with dopamine antagonists for reasons such as nausea or lactation difficulties develop psychotic symptoms when these medications are abruptly stopped.17–19 Non-­psychotic withdrawal effects (e.g. insomnia, agitation and anxiety) may also precipitate genuine relapse that would not have occurred in the absence of antipsychotic dose reduction (perhaps clumsily named withdrawal-­associated relapse).20 In patients with psychotic disorders, relapse often occurs when antipsychotics are withdrawn. This has been widely thought to represent an unmasking of the underlying chronic illness, but the nature of the process of withdrawing antipsychotics may itself be causally related to relapse.7 This suggestion is supported by the marked preponderance of relapses soon after abrupt antipsychotic cessation in patients with schizophrenia. In one analysis 60% of all relapses over 4 years occurred within 3 months of drug cessation,21 the time most likely for withdrawal effects to be evident. The idea that speed of stopping is an influence on relapse is also supported by evidence that slower tapering can reduce the rate of relapse.22,23 Withdrawal effects can be delayed in onset for weeks and sometimes months, for reasons that are poorly understood.20