Akathisia perphenazine

Akathisia, Parkinson-like syndrome, galactorrhea, and amenorrhea are side effects of perphenazine, caused by... 

The answer is c. (Hardman, pp 414-4163) Unwanted pharmacologic side effects produced by phenothiazine antipsychotic drugs (e.g., perphenazine) include Parkinson-like syndrome, akathisia, dystonias, galactorrhea, amenorrhea, and infertility. These side effects are due to the ability of these agents to block dopamine receptors. The phenothiazines also block muscarinic and a-adrenergic receptors, which are responsible for other effects. 

A 52-year-old woman developed Meige s syndrome 2 days after the appearance of akathisia. She had taken neuroleptic drugs for years, but her current medication had been changed to bromperidol 18 mg/day and trihexyphenidyl (benzhexol) 6 mg/day 2 days later she developed akathisia. Oral perphenazine 12 mg and trihexyphenidyl 6 mg dose-dependently reduced the frequency of blepharospasm the dosages of bromperidol and trihexyphenidyl were gradually reduced to 8 mg/ day and 3 mg/day respectively over 3 months, by which time her symptoms had completely disappeared. 

In a few cases, marked extrapyramidal side-effects (akathisia, dystonia, and parkinsonism) have been reported with flupbenazine, perphenazine, sulpiride, and thiothixene when fluoxetine is added to the regimen. The mechanism is speculated to be the result of fluoxetine-induced further suppression of dopaminergic activity in the nigrostriatal pathways (serotonergic stimulation leads to decreased dopamine release), in addition to increases in their plasma concentration. Fluoxetine has been shown to increase haloperidol serum levels by about 20%, presumably via inhibition of cytochrome P450 enzymes. Fluoxetine can increase the risk of seizure induction when added to clozapine due to an increase in clozapine serum levels, or by additive effects. Concomitant treatment with fluoxetine and risperidone is associated with a mean 4-fold increase in the plasma concentration of risperidone. ... 

Paroxetine. The effects of a single 100-microgram/kg oral dose of perphenazine on the performance of psychomotor tests were assessed after 4, 6, 8 and 10 hours in 5 subjects. The tests were then repeated after the subjects also took paroxetine 20 mg daily for 10 days. The scores for these tests were worsened by the perphenazine when compared with a placebo and further worsened by the presence of the paroxetine. In addition to over-sedation and impairment of the performance of psychomotor tests and memory, 2 of the subjects developed akathisia 10 hours after taking both drugs. The AUC of the perphenazine was increased sevenfold and the maximum plasma levels sixfold. ... 

Drug-drug interactions A case of an elderly female on perphenazine who experienced extraypyramidal symptoms and akathisia following the coadministration of terbenafine (a CYP2D6 inhibitor) is reported [199 ]. 

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