Differential Withdrawal Symptoms of Typical and Atypical Antipsychotics: A Narrative Review

Antipsychotics (APs) reduce abnormal neurotransmitter activity and treat mental conditions. However, APs can cause withdrawal symptoms, which can disrupt normal physiology. This research aimed to evaluate the APs' withdrawal symptoms and their evidence-based management. In the current review, forty-six papers were included after careful evaluation. All studies comparing the withdrawal symptoms between typical and atypical APs were included, while those focusing solely on safety were excluded. Quality and strength of evidence were also evaluated by standardised criteria. Abrupt discontinuation of typical APs results in dopaminergic rebound, causing motor symptoms. The aberrant discontinuation of atypical APs results in rebounds of dopaminergic, serotonergic, and cholinergic systems, leading to emotional dysregulation. Withdrawal symptoms must be managed by considering individual drug mechanisms as well as the demographics of patients. Clozapine withdrawal is associated with fewer side effects when tapered gradually over six months; risperidone discontinuation requires careful monitoring for dose-dependent extrapyramidal symptoms. Adolescents using olanzapine exhibit higher withdrawal-related morbidity compared to other age groups. Prolonged tapering of quetiapine has been shown to effectively mitigate withdrawal symptoms. Patients discontinuing aripiprazole experience mood swings due to its partial agonist effects on dopamine receptors; abrupt discontinuation of ziprasidone can lead to rebound psychosis and increased anxiety. The discontinuation of APs over a prolonged period shows improved patient outcomes; however, the period for discontinuation should be tailored to the individual patient's needs and the medication used. A holistic approach to tapered discontinuation can improve medical and psychosocial outcomes.