Sertraline in adults with pervasive developmental disorders: a prospective open-label investigation.

The short-term efficacy and tolerability of sertraline for adults with pervasive developmental disorders (PDDs) were assessed in this investigation. Forty-two adults with PDDs (autistic disorder, N = 22; Asperger's disorder, N = 6; and PDD not otherwise specified [NOS], N = 14) participated in a 12-week, open-label, systematic trial of sertraline. Behavioral ratings of repetitive symptoms, aggression, and social relatedness were obtained at baseline and after 4, 8, and 12 weeks of sertraline administration. Twenty-four (57%) of 42 patients showed significant improvement, primarily in repetitive and aggressive symptoms. Statistically significant changes in measures of social relatedness did not occur. Patients with autistic disorder and PDD NOS did significantly better than those with Asperger's disorder. Based on global improvement item criteria from the Clinical Global Impression Scale, 15 of 22 (68%) patients with autistic disorder, none of six (0%) patients with Asperger's disorder, and 9 of 14 (64%) patients with PDD NOS were categorized as treatment responders. Sertraline was well tolerated; no adverse cardiovascular effects, extrapyramidal symptoms, or seizures were identified. These findings suggested that sertraline may be an effective treatment for interfering repetitive and aggressive symptoms in adults with PDDs. Definitive statements about the efficacy and tolerability of sertraline for treating adults with PDDs must await results from double-blind, placebo-controlled trials. These preliminary results should not be generalized to include children and adolescents with PDDs.

Clomipramine in adults with pervasive developmental disorders: a prospective open-label investigation.

The purpose of this investigation was to determine the short-term efficacy and tolerability of clomipramine in a consecutive series of adults with pervasive developmental disorders (PDDs). Thirty-five adults with PDDs (DSM-IV), 16 of whom were nonverbal, entered a 12-week prospective open-label trial of clomipramine. The initial sample included 18 patients with autistic disorder, 6 patients with Asperger's disorder, and 11 patients with pervasive developmental disorder not otherwise specified (PDDNOS). Behavioral ratings were obtained at baseline and after 4, 8, and 12 weeks of clomipramine. Eighteen (55%) of the 33 patients who completed the trial were categorized as treatment responders based on scores of "much improved" or "very much improved" on the Clinical Global Impression (CGI) global improvement item (p < 0.001). Ten (63%) of 16 patients with autistic disorder, 2 (33%) of 6 patients with Asperger's disorder, and 6 (55%) of 11 patients with PDDNOS were considered responders to clomipramine treatment. In those 18 patients, clomipramine significantly reduced total repetitive thoughts and behavior (p < 0.001) and also aggression (p < 0.001), and improved some aspects of social relatedness, such as eye contact and verbal responsiveness (p < 0.001). Change in these specific symptom clusters over time was not related to DSM-IV subtype of PDD. The level of autistic behavior, as measured by the Autism Behavior Checklist (ABC) score, and full-scale intelligence quotient (IQ) were not significantly associated with global treatment response. Whereas clomipramine was well tolerated by most patients, 13 had clinically significant adverse effects. Three patients had seizures during clomipramine treatment, including 2 who had prior seizure disorders and were taking anticonvulsants. Of the 32 patients who had no history of prior seizures, only 1 had a seizure during clomipramine treatment. There were no adverse cardiovascular or extrapyramidal effects. All responders continued on clomipramine after completion of the study. The results of this open-label trial suggest that clomipramine may be an effective drug for reducing repetitive thoughts and actions and aggressive behavior and for improving some elements of social behavior, such as eye contact and verbal responsivity in adults with PDDs. Careful monitoring of adverse effects, particularly seizures, is warranted. Although an electroencephalogram (EEG) is not mandatory in patients with PDD prior to clomipramine treatment, we recommend that patients with PDD and a history of seizures be treated initially with a selective serotonin uptake inhibitor rather than with clomipramine. The findings of this study require replication in a double-blind placebo-controlled investigation before definitive statements of efficacy and tolerability can be made.

Effects of tryptophan depletion in drug-free adults with autistic disorder.

BACKGROUND: The primary objective of this study was to investigate the behavioral and biochemical responses to acute tryptophan depletion in drug-free adult patients with autistic disorder. METHODS: Twenty drug-free adults with autistic disorder (16 men and 4 women) (mean [+/- SD] age, 30.5 +/- 8.5 years) underwent short-term tryptophan depletion in a double-blind, placebo-controlled, randomized crossover design. Patients received a 24-hour, low-tryptophan diet followed the next morning by an amino acid drink. Behavioral ratings were obtained on the morning of the amino acid drink (baseline) and 180, 300, and 420 minutes after the drink. Plasma free and total tryptophan levels were obtained at baseline and 5 hours after the drink. The active and sham testing sessions were separated by 7 days. RESULTS: Eleven (65%) of the 17 patients who completed both test days showed a significant global worsening of behavioral symptoms with short-term tryptophan depletion, but none of the 17 patients showed any significant change in clinical status from baseline after sham depletion (P = .001). Tryptophan depletion led to a significant increase in behaviors such as whirling, flapping, pacing, banging and hitting self, rocking, and toe walking (P < .05). In addition, patients were significantly less calm and happy and more anxious. No significant change was observed in social relatedness or repetitive thoughts and behavior. Plasma total and free tryptophan levels were reduced 86% and 69%, respectively, 5 hours after the tryptophan-deficient amino acid drink. Patients who had a significant global exacerbation of symptoms had significantly higher baseline plasma total tryptophan levels (P < .001) and Autism Behavior Checklist scores (P = .005) than did patients who showed no significant change in symptoms after tryptophan depletion. CONCLUSIONS: The results of this study are consistent with previous research that has implicated a dysregulation in serotonin function in some patients with autism. These data suggest that the short-term reduction of serotonin precursor availability may exacerbate some symptoms characteristic of autism in some patients. Continued investigation into the role of serotonin in the pathogenesis and treatment of autistic disorder is warranted.

A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder.

BACKGROUND: Autistic disorder is characterized by a fundamental disturbance in social interaction, impairments in communication, and a markedly restricted repertoire of activities and interests. Abnormalities in the serotonin neurotransmitter system have been identified in some persons with autism. No consistently effective and safe drugs have been developed for treating the symptoms of autism. METHODS: Thirty adults with autistic disorder completed a 12-week double-blind, placebo-controlled trial of the potent and selective serotonin uptake inhibitor fluvoxamine maleate. Behavioral ratings were obtained at baseline and after 4, 8, and 12 weeks of treatment. RESULTS: Eight (53%) of 15 patients in the fluvoxamine-treated group were categorized as responders compared with none of 15 in the placebo group (P = .001). Fluvoxamine was superior to placebo in reducing repetitive thoughts and behavior (P < .001), maladaptive behavior (P < .001), and aggression (P < .03), and in improving some aspects of social relatedness (P < .04), especially language usage (P < .008). Treatment response was not correlated with age level of autistic behavior, or full-scale IQ. Other than mild sedation and nausea in a few patients, fluvoxamine was well tolerated. No dyskinesias, adverse cardiovascular events, or seizures occurred. CONCLUSIONS: Fluvoxamine is more effective than placebo in the short-term treatment of the symptoms of autistic disorder in adults. Controlled studies of fluvoxamine and other potent and selective serotonin uptake inhibitors seem warranted in children and adolescents with autism.

A case-controlled study of repetitive thoughts and behavior in adults with autistic disorder and obsessive-compulsive disorder.

OBJECTIVE: The purpose of this study was to investigate the types of repetitive thoughts and behavior demonstrated by adults with autistic disorder and compare them with those of age- and sex-matched adults with obsessive-compulsive disorder. METHOD: Fifty consecutive patients admitted to the Yale Adult Pervasive Developmental Disorders (Autism) Clinic with a primary diagnosis of autistic disorder (DSM-III-R and DSM-IV) completed the symptom checklist of the Yale-Brown Obsessive Compulsive Scale. Types of current obsessions and compulsions were evaluated. The comparison group consisted of 50 age- and sex-matched adults with obsessive-compulsive disorder (without tics) (DSM-III-R and DSM-IV). RESULTS: Direct discriminant function analysis showed that the patients with autistic disorder could be distinguished from those with obsessive-compulsive disorder on the basis of the types of current repetitive thoughts and behavior that they demonstrated. Compared to the obsessive-compulsive group, the autistic patients were significantly less likely to experience thoughts with aggressive, contamination, sexual, religious, symmetry, and somatic content. Repetitive ordering; hoarding; telling or asking (trend); touching, tapping, or rubbing; and self-damaging or self-mutilating behavior occurred significantly more frequently in the autistic patients, whereas cleaning, checking, and counting behavior was less common in the autistic group than in the patients with obsessive-compulsive disorder. In addition, a specific subset of seven obsessive-compulsive variables from the Yale-Brown Obsessive Compulsive Scale symptom checklist was identified that reliably predicted membership in the autistic group. CONCLUSIONS: These results suggest that the repetitive thoughts and behavior characteristics of autism differ significantly from the obsessive-compulsive symptoms displayed by patients with obsessive-compulsive disorder. Future studies are warranted to assess the treatment response and neurobiological underpinnings of repetitive thoughts and behavior in patients with autism and obsessive-compulsive disorder.