Extrapyramidal symptoms treatment

Trihexyphenidyl (Artane) and benztropine (Cogentin) are prescription drugs used in the treatment both of Parkinson s disease and the extrapyramidal side effects produced by neuroleptic medication. They are occasionally abused for their mind-altering properties, which occur at toxic doses (Perry et al. 1978). Abusers often try to obtain these drugs by false representation of extrapyramidal symptoms, which are claimed to result from the use of phenothi-azines or other neuroleptics (Rubinstein 1978). 

A metaanalysis showed that 17% to 18% of dementia patients showed a modest treatment response to atypical antipsychotics. Adverse events included somnolence, extrapyramidal symptoms, abnormal gait, worsening cognition, cerebrovascular events, and increased risk of death. 

Use in combination with lithium or valproate for the acute treatment of mania or mixed states Antagonist of postsynaptic DA2 receptors atypical agents also block 5-HT2a receptors that increase the presynaptic release of DA thus lowering the risk of extrapyramidal symptoms and prolactin release... 

We prefer low doses of atypical antipsychotics as a first-line treatment. In this way, the threat of extrapyramidal symptoms is largely avoided without having to use a second anticholinergic medication to offset antipsychotic side effects. Risperidone 0.25-0.5mg/day, olanzapine 2.5mg/day, quetiapine 25mg/day, ziprasidone 20mg/day, or aripiprazole 2.5-5mg/day are reasonable starting doses. The typically higher doses used to treat schizophrenia are usually not necessary. 

In addition to parkinsonism, another extrapyramidal side effect is the so-called acute dystonic reaction in which muscles (usually of the face or neck) go into an acute spasm. A dystonic reaction is painful and unpleasant, usually occurs early in treatment, and sometimes occurs after the very first dose of an antipsychotic. Another extrapyramidal symptom is akathisia, a restless inability to relax and sit still. Akathisia can range from a mild restlessness to extreme agitation. Rarely, patients have been known to attempt suicide during severe episodes of akathisia. It is easy to overlook akathisia, because it can easily be mistaken for a worsening of psychosis or anxiety. 

Extrapyramidal symptoms (EPS) Dystonic reactions develop primarily with the use of traditional antipsychotics. EPS has occurred during the administration of haloperidol and pimozide frequently, often during the first few days of treatment. Neuroleptic malignant syndrome (NMS) A potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, rhabdomyolysis, and acute renal failure. 

Extrapyramidal symptoms Extrapyramidal symptoms, manifested primarily as acute dystonic reactions, occur in approximately 0.2% to 1% of patients treated with the usual adult dosages of 30 to 40 mg/day. These usually are seen during the first 24 to 48 hours of treatment, occur more frequently in children and young adults, and are even more frequent at the higher doses used in prophylaxis of vomiting caused by cancer chemotherapy. If symptoms occur, they usually subside following 50 mg diphenhydramine IM. Benztropine 1 to 2 mg IM may also be used to reverse these reactions. 

Most antipsychotics and especially the piperazines and the butyrophenones can cause extrapyra-midal symptoms. Blockade of dopamine receptors mainly in the corpus striatum is held responsible for these extrapyramidal effects. They may become manifest as a variety of clinical symptoms and it should be noted that within 24 8 hours after the beginning of treatment acute dystonic reactions like torticollis, facial grimacing and opisthotonos may occur. Parkinsonism-like symptoms such as bradyki-nesia, rigidity and tremor occur after weeks or months of therapy and are more common in the elderly. Motor restlessness, i.e. akathisia, also mostly occurs not before weeks or months after starting therapy. The tendency of an antipsychotic agent to produce extrapyramidal symptoms appears to be inversely related to its ability to block cholinergic receptors. 

The most troublesome untoward effects of treatment with reserpine involve the CNS. Sedation and depression are the most common, although nightmares and thoughts of suicide also occur. Reserpine treatment, therefore, is contraindicated in patients with a history of severe depression. The occasional report of re-serpine-induced extrapyramidal symptoms, which are similar to those seen in patients with Parkinson s disease, is believed to be a result of dopamine depletion from neurons in the CNS. 

Unlabeled Uses Treatment of Alzheimer s disease, attention-deficit-hyperactivity disorder, depression, early Parkinson s disease, extrapyramidal symptoms, negative symptoms of schizophrenia... 

Blitzstein, S.M. and Brandt, G.T. (1997) Extrapyramidal symptoms from intravenous haloperidol in the treatment of delirium. Am Psychiatry 154 1474-1475. 

The four drugs were administered by psychiatrists blinded to treatment group assignment of patients. The 14-week study consisted of an 8-week dose escalation and fixed dose and a 6-week variable-dose period. The mean dose levels (mg/day) of the four compounds after the first 8 weeks were 452 for clozapine. 20.2 for olanzapine. 8.3 for risperidone and 19.6 for haloperidol. Patients on haloperidol received prophylactic anticholinergic medication to prevent extrapyramidal symptoms, and a few other drugs were permitted to treat agitation and insomnia. 

The synthesis and discovery of the antipsychotic effects of the piperazinyl-dibenzoazepine, clozapine (Fig. 13.1) and its launch in 1972 was an important turning point in the drug treatment of schizophrenia [1-3]. Clozapine was called an atypical antipsychotic as it did not produce side effects characteristic for compounds of the chlorpromazine- or haloperidol-type (i.e., extrapyramidal symptoms) either in animal models or in the clinic. Its use, however, became very limited when it was recognized that clozapine might cause a severe, and sometimes fatal, form of agranulocytosis. 

Extrapyramidal symptoms (including akathisia, dystonia, dyskinesia, tardive dyskinesia, parkinsonism, and brux-ism) have been reported in association with SSRIs, especially in the presence of predisposing factors (SEDA-14, 14 12). Current data suggest that SSRIs should be used with caution in patients with parkinsonism (see the monograph on fluoxetine). Concomitant treatment with neuroleptic drugs and high concentrations of SSRIs seems to predispose to extrapyramidal symptoms. Elderly patients and women are also at increased risk. 

Gill HS, DeVane CL, Risch SC. Extrapyramidal symptoms associated with cyclic antidepressant treatment a review of the literature and consolidating hypotheses. J Clin Psychopharmacol 1997 17(5) 377-89. 

Extrapyramidal symptoms have been identified at much higher rates in psychotic youths than in comparable adult populations (194). Subjects who selected because of prominent positive psychotic symptoms were randomly assigned to double-blind, parallel treatment with risperidone (mean age 15 years mean dose at termination 4 mg n = 19), olanzapine (mean age, 14.6 years mean dose at termination, 12.3 mg n = 16) or haloperidol (mean age 15 years mean dose at termination 5 mg n = 15) for 8 weeks in all, 88% of those who took olanzapine, 74% of those who took risperidone, and 53% of those who took... 

Several reports have suggested a higher incidence and severity of extrapyramidal symptoms during haloperidol treatment in congenitally poor metabolizers of substrates... 

Suenaga T, Tawara Y, Goto S, Kouhata SI, Kagaya A, Horiguchi J, Yamanaka Y, Yamawaki S. Risperidone treatment of neuroleptic-induced tardive extrapyramidal symptoms. Int J Psychiatry Chn Pract 2000 4 241-3. 

In a retrospective study in 499 in-patients with schizophrenia or schizoaffective disorder (39) 259 subjects were taking olanzapine and 240 risperidone. Treatment was considered effective in most cases (74% with olanzapine and 78% with risperidone). There were adverse effects in 19% of the patients taking olanzapine and 22% of those taking risperidone they were mainly somnolence (n = 15 and n = 17 respectively) and extrapyramidal symptoms (n = 9 and n = 6 respectively) there were also three cases of weight gain with olanzapine. 

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