Haloperidol withdrawal symptoms
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Haloperidol Withdrawal Symptoms: An Overview
Introduction to Haloperidol Withdrawal
Haloperidol, a potent antipsychotic medication, is widely used for treating various psychiatric conditions, including schizophrenia and acute psychosis. However, discontinuation of haloperidol can lead to a range of withdrawal symptoms, which can be both physical and psychological. This article synthesizes findings from multiple studies to provide a comprehensive overview of haloperidol withdrawal symptoms.
Physical Withdrawal Symptoms
Movement Disorders and Dyskinesia
One of the most notable physical withdrawal symptoms of haloperidol is the emergence of movement disorders. Studies have documented cases of self-limited dyskinesia, characterized by involuntary muscle movements, during the withdrawal of high-dose intravenous haloperidol therapy in ICU patients2. Additionally, withdrawal emergent syndrome (WES), a subtype of tardive dyskinesia, has been observed in infants born to mothers who were on haloperidol therapy during pregnancy. Symptoms included repeated tongue thrusting, abnormal hand posturing, and tremors8.
Gastrointestinal and Autonomic Symptoms
Physical symptoms of haloperidol withdrawal also include gastrointestinal issues such as stomach pains and indigestion, as well as autonomic symptoms like sweating and nausea4. These symptoms are often accompanied by increased irritability, nervousness, and moodiness3.
Psychological Withdrawal Symptoms
Anxiety and Depression
Abrupt discontinuation of haloperidol can lead to significant psychological distress. Anxiety and depression are common, and there is evidence suggesting that what is often perceived as a "relapse into psychosis" may actually be withdrawal-induced anxiety and depression4. This anxiogenic component of withdrawal has been supported by animal studies, where rats exhibited anxiety-like behaviors after haloperidol withdrawal4.
Behavioral Changes
Behavioral changes are also prominent during haloperidol withdrawal. Patients may experience increased oppositional behaviors, mood instability, and hyperactivity. Interestingly, some studies have noted that while withdrawal can exacerbate certain symptoms like motor tics in Tourette Syndrome patients, it can also lead to a reduction in depressive and obsessive-compulsive symptoms3.
Biochemical and Neurological Changes
Dopamine and GABAergic Systems
Chronic haloperidol treatment and subsequent withdrawal result in significant biochemical alterations. Long-term use of haloperidol leads to dopamine receptor supersensitivity, which is evident from enhanced stereotypic behaviors in animal models6. Additionally, withdrawal is associated with increased levels of gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase activity, which further inhibit dopamine release6.
Cholinergic Supersensitivity
Withdrawal from haloperidol, a neuroleptic with weak anticholinergic effects, has been linked to cholinergic supersensitivity. This phenomenon is characterized by a rebound increase in cholinergic activity, leading to symptoms such as depression of locomotor activity and lowered seizure thresholds9.
Conclusion
Haloperidol withdrawal can lead to a complex array of symptoms, ranging from movement disorders and gastrointestinal issues to anxiety and depression. These symptoms are underpinned by significant biochemical changes in the brain's dopaminergic and GABAergic systems. Understanding these withdrawal symptoms is crucial for clinicians to manage discontinuation of haloperidol effectively and to mitigate the adverse effects associated with its withdrawal. Further research is needed to develop strategies for safer discontinuation protocols and to explore potential treatments for withdrawal symptoms.
Sources and full results
Most relevant research papers on this topic
Effectiveness and Safety of Haloperidol Add-on Methadone in Acute Opium Withdrawal Symptoms of Opioid-dependent Patients: A Double-blind Randomized Placebo-controlled Clinical Trial
Haloperidol combined with methadone effectively reduces opioid withdrawal symptoms in patients with low dose opioid consumption, but larger controlled trials are needed for widespread application.
RCT
Rigorous JournalMovement disorders associated with withdrawal from high-dose intravenous haloperidol therapy in delirious ICU patients.
High-dose intravenous haloperidol therapy in ICU patients can cause self-limited dyskinesia in delirious patients, highlighting the need for caution during withdrawal.
Case ReportIntermittent medication cessation in the treatment of Tourette Syndrome
Intermittent medication cessation in Tourette Syndrome patients may increase symptoms but may also reduce depression, obsessive-compulsive symptoms, hyperactivity, and social withdrawal.
Observational StudyWithdrawal from chronic haloperidol substitutes for the pentylenetetrazol discriminative stimulus.
Chronic haloperidol withdrawal in rats involves anxiogenic components, suggesting that abrupt discontinuation of psychoactive therapeutic agents may result in anxiety.
Non-RCT
Animal StudyDifferences between haloperidol- and pimozide-induced withdrawal syndrome: a role for Ca2+ channels.
Haloperidol-induced withdrawal syndrome involves increased cortical Ca2+ channel and limbic dopamine D1 receptor density, while pimozide-induced withdrawal syndrome is associated with no biochemical changes and depressed locomotor activity.
Non-RCTAnimal StudyBehavioural and biochemical alterations following haloperidol treatment and withdrawal: The animal model of tardive dyskinesia reexamined
Chronic haloperidol treatment and withdrawal lead to behavioral dopamine supersensitivity and biochemical alterations in the dopaminergic and GABAergic systems, with these changes interrelated.
Non-RCTAnimal StudyEnhancement of alcohol withdrawal convulsions in mice by haloperidol.
Haloperidol may enhance alcohol withdrawal convulsions, and chlordiazepoxide appears to be a more effective and safer agent for treating excitation symptoms.
Withdrawal emergent syndrome in an infant associated with maternal haloperidol therapy.
Maternal haloperidol therapy during pregnancy can cause withdrawal emergent syndrome in infants, causing tongue thrust, abnormal hand posturing, and tremors.
Case ReportThe role of cholinergic supersensitivity in the medical symptoms associated with withdrawal of antipsychotic drugs.
Neuroleptic withdrawal symptoms are more likely due to rebound cholinergic hypersensitivity, rather than dopamine-blocking activity, rather than the drug's dopamine-blocking activity.
Literature ReviewEffects of haloperidol on peripheral erythrocytes and brain neurotransmitter levels of juvenile African catfish, Clarias gariepinus (Burchell 1822).
Haloperidol is toxic to juvenile African catfish, reducing serotonin activity and increasing dopamine activity, but some parameters recover after a 5-day withdrawal period.
Non-RCTAnimal Study