Neuroleptic Withdrawal Symptoms

Withdrawal symptoms often include a temporary worsening of dys-kinetic effects, both painful and frightening. As documented in chapter 5, withdrawal from neuroleptics commonly produces a level of emotional suffering and disturbance more severe than anything the individual experienced prior to starting the medication. In adults, this frequently manifests as psychotic symptoms worse than anything experienced prior to starting on the medication. In children, it can result in very disturbed behavior. 

How to withdraw from psychiatric drugs is discussed in chapter 15. 

---

Clozapine withdrawal symptoms occur after stopping therapeutic doses (range 200 to 900 mg/day) administered from 4 months to several years. In a study, one-third of patients who were switched directly from clozapine to risperidone remained stable, one-third had to be switched back to clozapine, and one-third were treated with combined risperidone-clozapine or risperidone-neuroleptic ( 480). 

Because of the withdrawal symptoms, it is often necessary to reduce neuroleptic drugs at a very slow rate. Sometimes withdrawal seems to become impossible. I describe the principles of safely withdrawing from psychiatric drugs in chapter 15. 

Many neuroleptics produce withdrawal symptoms that mimic the flu, including emotional upset, insomnia, nausea and vomiting, diarrhea, anorexia and weight loss, and muscle aches (chapter 4). This is particularly strong in drugs that have anticholinergic properties such as Thorazine and Mellaril. 

Worsening of psychotic symptoms and/or dyskinetic movements can occur when dosages are lowered or a neuroleptic drug is withdrawn. A functional increase in mesolimbic and striatal dopaminergic sensitivity has been suggested as an explanation (550). Psychotic relapse is rarely seen in the first 2 weeks after withdrawal, but physical withdrawal symptoms generally begin within 48 hours of the last dose (SEDA-14, 54). 

Rare Hepatic toxicity tinnitus bone marrow depression, including agranulocytosis seizures peripheral neuropathy severe cardiovascular effects in patients with cardiac disease photosensitivity dysarthria smttering withdrawal symptoms nausea, tremor, anorgasmia, and seizures may be more common with clomipramine tardive dyskinesia and neuroleptic malignant syndrome with amoxapine renal failure with overdosage of amoxapine... 

Neuroleptics or antipsychotics suppress the positive symptoms of schizophrenia such as combativeness, hallucinations and formal thought disorder. Some also alleviate the negative symptoms such as affective blunting, withdrawal and seclusiveness. Neuroleptics also produce a state of apathy and emotional indifference. Most neuroleptics block dopamine D2-receptors but some, like clozapine, also block dopamine D4-receptors or serotonin 5-hydroxytryptamine2A-receptors. 

Intrathecal - Early symptoms of baclofen withdrawal may include return of baseline spasticity, pruritus, hypotension, and paresthesias. Some clinical characteristics of the advanced intrathecal baclofen withdrawal syndrome may resemble autonomic dysreflexia, infection (sepsis), malignant hyperthermia, neuroleptic-malignant syndrome, or other conditions associated with a hypermetabolic state or widespread rhabdomyolysis. 

Tapering of dose Cases of a symptom complex resembling neuroleptic malignant syndrome characterized by elevated temperature, muscular rigidity, altered consciousness, and elevated creatine phosphokinase (CPK) have been reported in association with the rapid dose reduction or withdrawal of other dopaminergic drugs. 

Acute dystonic reactions occurring following the administration of potent neuroleptics are reported primarily in young men and usually develop shortly after the start of therapy. By contrast, tardive dystonia occurs following chronic neuroleptic treatments as with tardive dyskinesia, symptoms often begin after the abrupt withdrawal of the neuroleptic. Although less severe than acute dystonic reactions, tardive dystonia is frequently permanent and difficult to treat. 

Furthermore, at the times they were being evaluated, the patients continued to take the olanzapine, which, like all neuroleptics, suppresses the appearance of TD symptoms while at the same time causing or worsening the underlying disorder (see subsequent section). Therefore, the only way to determine an accurate rate of TD is to withdraw the patients from the offending drug before the final evaluation. In this study, the actual rate of TD would have been much higher than 3% per year if the patients had been withdrawn from the olanzapine before the final TD evaluation. 

---