Research Units on Pediatric Psychopharmacology (RUPP) Autism Network. Background and rationale for an initial controlled study of risperidone.

This article has reviewed the background and rationale for the choice of risperidone as the first drug to be studied by the RUPP Autism Network. Risperidone has potent effects on 5-HT and DA neuronal systems, both of which have been implicated in the pathophysiology of autism. Unlike the typical antipsychotics, haloperidol and pimozide, which have been shown to be effective for reducing many of the maladaptive behaviors associated with autism, risperidone's 5-HT2A/DA D2 ratio of receptor blockade appears to produce a lower risk of acute and chronic extrapyramidal side effects, as well as enhanced efficacy for the "negative" symptoms of autism. Indirect clinical and preclinical evidence supports the use of risperidone to treat impaired social behavior, interfering repetitive phenomena, and aggression, targets of pharmacotherapy for many patients with autism. Numerous published open-label trials in children and adolescents with autism and related PDDs and one double-blind, placebo-controlled study in adults suggest that risperidone has promise for the treatment of children and adolescents with autism. Because most of these studies have been short-term, open-label trials in small samples, however, a large-scale controlled study of risperidone in children and adolescents with autism is needed to confirm these results. Finally, because it is likely that children who demonstrate short-term benefit from risperidone will remain on the medication indefinitely, the longer-term effectiveness and safety of risperidone in this population also needs to be determined. The design of this study and the assessments used are described separately.

Serotonergic antidepressants and urinary incontinence.

Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.

Clinical correlates of valproate augmentation in refractory bipolar disorder.

We examined the clinical correlates of valproate (VPA) therapy in refractory bipolar disorder. Retrospective chart review was used to collect demographic and clinical data including present diagnosis, diagnosis at illness onset, duration of illness, number of hospitalizations, VPA dose, side effects, and maximum serum concentration. Global response was rated once patients serum VPA exceeded 50 mg/dL. The charts of all inpatients admitted over a two-year period and treated with VPA for acute episodes of bipolar disorder in manic, mixed, or depressed phase were reviewed. Seventeen of these patients began VPA augmentation while hospitalized and became the cohort for review. Patients were excluded if VPA was started prior to admission or the patient was discharged less than one week after drug initiation. Patients were not excluded on the basis of EEG, CT, or neurological exam findings. Overall, 12 of 17 (71%) of the patients showed a moderate or marked improvement while 5 of 17 (29%) showed mild or no response. Responders were older and had a longer duration of illness with an increased number of hospitalizations. There was a strong trend for responders to achieve a higher serum VPA level. A significant positive correlation was found between response in acute mania and psychotic symptoms at first episode of illness.

Does hair zinc predict amphetamine improvement of ADD/hyperactivity?

In 18 boys with ADHD (ages 6-12) in a balanced crossover design, parent and teacher hyperactivity rating differences between one month of dextroamphetamine and one month of placebo correlated significantly (p less than .05, 2 tailed) on Pearson's r with baseline hair zinc levels and nonsignificantly with 24-hour urinary zinc excretion. The signs of the correlations were such that a higher baseline zinc predicted a better placebo-controlled response to amphetamine. Patient baseline urinary zinc was significantly (p less than .02) lower than 7 normal controls. These findings are compatible with the possibility that some ADHD children may be mildly deficient in zinc and constitute poorer stimulant responders. Correlations of zinc levels with 24-hour urinary MHPG were in the expected direction but nonsignificantly by 2-tailed test.

Complications of phenylpropanolamine.

Phenylpropanolamine is a sympathomimetic agent present in over 100 proprietary and prescription anorectics, nasal decongestants, psychostimulants and treatments for premenstrual syndrome. It is often found in street drugs prepared to look like amphetamines. Phenylpropanolamine has precipitated paranoid psychosis, severe anxiety, cerebrovascular accidents and hypertensive crises. Hypertensive crises can be treated with phentolamine. Psychiatric symptoms and anxiety are managed with benzodiazepines.

Gamma-linolenic acid for attention-deficit hyperactivity disorder: placebo-controlled comparison to D-amphetamine.

In a Latin-square double-crossover with random assignment to sequence, 18 boys, aged 6-12 years, with attention-deficit hyperactivity disorder received 1 month each of placebo, D-amphetamine, and Efamol (evening primrose oil containing gamma-linolenic acid, with vitamin E as preservative). Parents' ratings were noncontributory. Teachers' ratings showed a trend of Efamol effect between placebo and D-amphetamine. The trend reached significance (p less than 0.05) only on Conners Hyperactivity Factor. Dosage may be crucial; 8 Efamol capsules per day were used in this study. Heuristic data scrutiny suggested possible interaction (sequence effect). Further study with a different design and dose is suggested. This study does not establish Efamol as an effective treatment.