Julie A. Cold

Seizure Activity Associated with Antipsychotic Therapy

Approximately one percent of patients receiving antipsychotic medications develop seizure activity. In addition, approximately seven percent of epileptic patients develop chronic psychosis requiring antipsychotic treatment. A history of antipsychotic-induced seizures in patients exhibiting florid psychosis should not preclude the use of antipsychotic medications. Different antipsychotics affect the seizure threshold in varying degrees, and the least epileptogenic agents should be selected for this population. Predisposing factors and other risk factors associated with antipsychotic-induced seizures are identified. Guidelines for the use of antipsychotic medications in psychotic patients with a history of seizures are presented.

Venlafaxine and Nefazodone, Two Pharmacologically Distinct Antidepressants

Venlafaxine, a phenylethylamine, and nefazodone, a phenylpiperazine compound, are the newest antidepressants to receive approval of the Food and Drug Administration and to be marketed in the United States. Both strongly inhibit serotonin (5‐HT) reuptake; venlafaxine also inhibits norepinephrine reuptake, and nefazodone also exhibits 5‐HT2‐receptor antagonism. Venlafaxine inhibits the cytochrome P‐450 2D6 isozyme to a lesser extent than the selective serotonin reuptake inhibitors (SSRIs) and is 27% protein bound. Structurally, the drugs are unrelated to SSRIs and have some clinically important differences in side effect profiles. Nausea, headache, somnolence, and dry mouth are the most frequently reported side effects with both. Sustained hypertension was reported by a limited number of venlafaxinetreated patients.

NeuRecover-SA™ in the Treatment of Cocaine Withdrawal and Craving

SummaryThe efficacy of NeuRecover-SA™ (formerly called Tropamine+™, and TropaGen™) in the treatment of cocaine withdrawal and craving was evaluated at a state psychiatric hospital. This double-blind, placebo-controlled study was conducted in hospitalised patients with a DSM-III-R diagnosis of cocaine dependence. Eight patients received NeuRecover-SA™ and 4 patients received placebo. No significant difference in patient demographics was found. The mean number of abstinent symptoms (± SEM) declined over the first 4 days of treatment, 10.63 ± 1.32 on day 1 vs 4 ± 1.65 on day 4 in the NeuRecover-SA™ group compared with 7.25 ± 2.93 on day 1 vs 4.25 ± 3.61 on day 4 in the placebo group. Cocaine craving in the NeuRecover-SA™ group on day 1 was 7.88 ± 1.22 vs 2.71 ± 1.22 on day 4 and 5 ± 2.89 on day 1 vs 2 ± 1.68 on day 4 in the placebo group. A Mann-Whitney U test showed no statistically significant differences in abstinent symptomatology between or within treatment groups, or treatment effect in the placebo group. However, a significant decrease (p < 0.05) in cocaine craving occurred in the NeuRecover-SA™ group.In conclusion, these preliminary results suggest that NeuRecover-SA™ reduces cocaine craving, and larger, longer term studies are warranted.

Effect of Cimetidine on the Pharmacokinetics of Alcohol in Social and Chronic Drinkers

SummarySeveral investigators have studied the drug-drug interaction that may exist when alcohol and H2-receptor antagonists (i.e. cimetidine, ranitidine, famotidine) are administered concomitantly. Results from these studies have been mixed. However, no systematic investigation of the change in blood alcohol concentrations in the social drinker versus the chronic drinker challenged by concurrent intake of alcohol and H2-receptor antagonist has been conducted.Eleven volunteers participated in this 14-day study. On day 0, study participants were administered an oral alcohol dose of 0.15 g/kg. On days 1 to 9, no medication was given. All volunteers then received cimetidine 400mg twice daily on days 10 to 13. On day 14, study participants received an oral alcohol dose of 0.15 g/kg after their morning dose of cimetidine. Blood sampling was performed on days 0 and 14 after alcohol administration.The comparative alcohol availabilities, pre- and post-cimetidine, were determined by comparing the time to peak plasma concentration (tmax), peak plasma concentration (Cmax), and the total area under the concentration-time curve (AUC). In the chronic drinkers, tmax was significantly shorter than in the social drinkers following cimetidine administration (p=0.008).Chronic drinkers who drink after cimetidine administration will have higher concentrations of alcohol faster than social drinkers. Medicolegal consequences resulting from this drug-drug interaction may occur; clinicians should therefore counsel patients about the possibility of enhanced impairment resulting from concurrent administration of these 2 drugs.

Possible Influence of Carbamazepine on Plasma: Imipramine Concentrations in Children with Attention

The effect of carbamazepine on the plasma concentration of imipramine and its metabolite desipramine was examined retrospectively in 36 sex- and age-matched children with attention deficit hyperactivity disorder. One-half of the children received imipramine and the other half received combined carbamazepine and imipramine for 1-6 months. The imipramine dosage was significantly higher in the combined treatment group than in the imipramine-only group. Despite receiving larger doses, the combined treatment group had significantly lower mean levels of imipramine, desipramine, and total tricyclic antidepressant compared with those children receiving imipramine alone. Lowered plasma concentrations of tricyclic antidepressants with carbamazepine coadministration have not been reported previously. Although more rigorous studies are needed to confirm these findings, our data suggest that increased imipramine doses may be necessary for adequate response in children on combined therapy. Moreover, toxicity could result upon withdrawal without imipramine dosage adjustment.