Neurocognitive impairment in unaffected siblings of youth with bipolar disorder.

BACKGROUND: There is growing evidence for the familiality of pediatric bipolar disorder (BPD) and its association with impairments on measures of processing speed, verbal learning and 'executive' functions. The current study investigated whether these neurocognitive impairments index the familial risk underlying the diagnosis. METHOD: Subjects were 170 youth with BPD (mean age 12.3 years), their 118 non-mood-disordered siblings and 79 non-mood-disordered controls. Groups were compared on a battery of neuropsychological tests from the Wechsler Intelligence Scales, the Stroop Color Word Test, the Wisconsin Card Sorting Test (WCST), the Rey-Osterrieth Complex Figure (ROCF), an auditory working memory Continuous Performance Test (CPT) and the California Verbal Learning Test-Children's Version (CVLT-C). Measures were factor analyzed for data reduction purposes. All analyses controlled for age, sex and attention-deficit/hyperactivity disorder (ADHD). RESULTS: Principal components analyses with a promax rotation yielded three factors reflecting: (1) processing speed/verbal learning, (2) working memory/interference control and (3) abstract problem solving. The CPT working memory measure with interference filtering demands (WM INT) was only administered to subjects aged > or =12 years and was therefore analyzed separately. BPD youth showed impairments versus controls and unaffected relatives on all three factors and on the WM INT. Unaffected relatives exhibited impairments versus controls on the abstract problem-solving factor and the WM INT. They also showed a statistical trend (p=0.07) towards worse performance on the working memory/interference control factor. CONCLUSIONS: Neurocognitive impairments in executive functions may reflect the familial neurobiological risk mechanisms underlying pediatric BPD and may have utility as endophenotypes in molecular genetic studies of the condition.

Pediatric mania: a developmental subtype of bipolar disorder?

Despite ongoing controversy, the view that pediatric mania is rare or nonexistent has been increasingly challenged not only by case reports, but also by systematic research. This research strongly suggests that pediatric mania may not be rare but that it may be difficult to diagnose. Since children with mania are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset mania may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. The major difficulties that complicate the diagnosis of pediatric mania include: 1) its pattern of comorbidity may be unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder, aggression, and conduct disorder; 2) its overlap with substance use disorders; 3) its association with trauma and adversity; and 4) its response to treatment is atypical by adult standards.

Does attention-deficit hyperactivity disorder impact the developmental course of drug and alcohol abuse and dependence?

BACKGROUND: The co-occurrence of attention-deficit hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD) in adults has been the focus of much clinical and scientific inquiry. In this study we examine the effects of ADHD on the transitions from substance abuse to dependence and between different classes of agents of abuse. METHODS: An ADHD sample of 239 consecutively referred adults of both genders with a clinical diagnosis of childhood-onset and persistent DSM-III-R ADHD confirmed by structured interview were compared with 268 non-ADHD healthy adults. RESULTS: ADHD was associated with a twofold increased risk for PSUD. ADHD subjects were significantly more likely than comparisons to make the transition from an alcohol use disorder to a drug use disorder (hazard ratio = 3.8) and were significantly more likely to continue to abuse substances following a period of dependence (hazard ratio = 4.9). CONCLUSIONS: ADHD is associated with a sequence of PSUD in which early alcohol use disorder increases the risk for subsequent drug use disorder, and early substance dependence increases the risk for subsequent substance abuse. If confirmed such developmental pathways might lead to preventive and early intervention strategies aimed at reducing the risk for PSUD in ADHD subjects.

Parsing pediatric bipolar disorder from its associated comorbidity with the disruptive behavior disorders.

The unique pattern of comorbidity found in pediatric mania greatly complicates accurate diagnosis, the course of the disorder, and its treatment. The pattern of comorbidity is unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder (ADHD), aggression, and conduct disorder. Clinically, symptoms of mania have been discounted as severe ADHD or ignored in the context of aggressive conduct disorder. This atypicality may lead to neglect of the mood component. The addition of high rates of additional disorders contributes to the severe morbidity, dysfunction, and incapacitation frequently observed in these children. A comprehensive approach to diagnostic evaluation is the keystone to establishing an effective treatment program because response to treatment differs with individual disorders. Recognition of the multiplicity of disorders guides therapeutic options in these often refractory conditions. What was previously considered refractory ADHD, oppositionality, aggression, and conduct disorder may respond after mood stabilization. We review these issues in this article.

A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults.

OBJECTIVE: Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, there is a paucity of controlled pharmacological trials demonstrating the effectiveness of compounds used in treatment, particularly nonstimulants. The authors report results from a controlled investigation to determine the anti-ADHD efficacy of bupropion in adult patients with DSM-IV ADHD. METHOD: This was a double-blind, placebo-controlled, randomized, parallel, 6-week trial comparing patients receiving sustained-release bupropion (up to 200 mg b.i.d.) (N=21) to patients receiving placebo (N=19). The authors used standardized structured psychiatric instruments for diagnosis of ADHD. To measure improvement, they used separate assessments of ADHD, depression, and anxiety symptoms at baseline and each weekly visit. RESULTS: Of the 40 subjects (55% male) enrolled in the study, 38 completed the study. Bupropion treatment was associated with a significant change in ADHD symptoms at the week-6 endpoint (42% reduction), which exceeded the effects of placebo (24% reduction). In analyses using a cutoff of 30% or better reduction to denote response, 76% of the subjects receiving bupropion improved, compared to 37% of the subjects receiving placebo. Similarly, in analyses using Clinical Global Impression scale scores, 52% of the subjects receiving bupropion reported being "much improved" to "very improved," compared to 11% of the subjects receiving placebo. CONCLUSIONS: These results indicate a clinically and statistically significant effect of bupropion in improving ADHD in adults. The results suggest a therapeutic role for bupropion in the armamentarium of agents for ADHD in adults, while further validating the continuity of pharmacological responsivity of ADHD across the lifespan.

Six-week, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder.

OBJECTIVE: Despite the increasing awareness of attention deficit hyperactivity disorder (ADHD) in adults, there are a limited number of controlled pharmacologic studies of this disorder; most of the trials have focused on the psychostimulants. Because the tricyclic anti-depressant desipramine has been found to be effective in treating ADHD in pediatric groups, the authors tested its efficacy in adults with ADHD. METHOD: The authors conducted a randomized, 6-week, placebo-controlled, parallel-design study of desipramine at a target daily dose of 200 mg in 41 adult patients with DSM-III-R ADHD. They used standardized structured psychiatric instruments for diagnosis and, as the dependent variables (outcome), used separate assessments of ADHD, depressive, and anxiety symptoms at baseline and at each biweekly visit. RESULTS: There were highly significant differences in the reduction of ADHD symptoms between adults receiving desipramine and placebo. Within the desipramine-treated group, there were clinically and statistically significant differences between baseline and the week 6 end point for 1) reduction of 12 of 14 symptoms of ADHD and 2) decreases in the broad categories of hyperactivity, impulsivity, and inattentiveness. In contrast, placebo-treated patients showed no differences between baseline and end point for any of the ADHD symptoms assessed. According to strict, predefined criteria for response, 68% of desipramine-treated subjects and no subjects in the placebo group were considered positive responders. Response to desipramine was independent of dose, level of impairment, gender, or lifetime psychiatric comorbidity with anxiety or depressive disorders. CONCLUSIONS: These results, similar to findings in children and adolescents with ADHD, indicate that desipramine is effective in the treatment of ADHD in adults.

A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder.

OBJECTIVE: Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, there is a paucity of controlled pharmacological trials. Recent reports have suggested the potential usefulness of cholinergic agents for ADHD. To this end, the authors completed a controlled study of ABT-418, a novel cholinergic activating agent, for the treatment of adults with ADHD. METHOD: This was a double-blind, placebo-controlled, randomized, crossover trial that compared a transdermal patch of ABT-418 (75 mg/day) to placebo in adults who met DSM-IV criteria for ADHD. There were two 3-week treatment periods separated by 1 week of washout. RESULTS: Of the 32 subjects enrolled in the study (88% were men; mean age = 40 years, SD = 9), 29 completed the study. At the endpoint of each active arm (last observation carried forward), a significantly higher proportion of subjects was considered improved while receiving ABT-418 than while receiving placebo (40% versus 13%). Similarly, at endpoint there was a significantly greater reduction in ADHD symptom checklist scores (28% versus 15%). Symptoms reflective of attention, and subjects with less severe ADHD, responded more robustly to ABT-418. Treatment with ABT-418 was relatively well tolerated; dizziness and nausea were the most frequently reported adverse effects. CONCLUSIONS: The results of this investigation indicate that ABT-418, a nicotinic analog, may be a potentially useful agent for the treatment of ADHD.

Dopamine D4 gene 7-repeat allele and attention deficit hyperactivity disorder.

OBJECTIVE: Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component, and some studies have reported an association between ADHD and the dopamine D4 (DRD4) gene. METHOD: The authors recruited 27 triads that comprised an ADHD adult, his or her spouse, and their ADHD child. These triads were assessed for ADHD, and their DNA was genotyped for DRD4 alleles. RESULTS: A multiallelic transmission disequilibrium test suggested an association between ADHD and the DRD4 7-repeat allele. Among family members, the number of 7-repeat alleles predicted the diagnosis of ADHD. CONCLUSIONS: Prior reports of an association between ADHD and DRD4 generalize to families recruited through clinically referred ADHD adults. However, because there are some conflicting studies, further work is needed to clarify the role of DRD4 in the etiology of the disorder.

Comparison of plasma cortisol and corticosterone in the dexamethasone suppression test for melancholia.

The suppression of plasma corticosterone (B), measured by radioimmunoassay (RIA), was compared to simultaneous suppression of plasma cortisol (F), measured as total corticoids by a competitive protein binding (CPB) assay, in the overnight dexamethasone suppression test (DST). Baseline plasma B concentrations in 10 control subjects were 4.04 +/- 1.07 ng/ml (X +/- S.D.) at 0800 hr and 1.51 +/- 0.68 ng/ml at 1600 hr. Post-dexamethasone 1600 hr B levels in the controls were 0.46 +/- 0.29 ng/ml. An early escape of plasma B (greater than 1.2 ng/ml), like that of F (greater than 5 micrograms/dl), during the overnight 24 hr 1.0 mg dose DST was noted in patients with melancholia (endogenous depression). Half-hourly catheter samples in a normal subject stimulated to escape from dexamethasone suppression showed that in general, plasma B concentrations parallel plasma F concentrations over a 12 hr period. Repeated weekly DSTs on two patients with different psychiatric diagnoses resulted in B : F correlations of 0.74 and 0.60. Overall agreement between B- and F-DST outcomes in all categories tested at 1600 and 2300 hr was 93%; the agreement in the melancholic and non-endogenous depressed groups was 100%. Post-dexamethasone, both B and F were suppressed 55-60% below the criterion level in controls. In those patients who escaped from dexamethasone suppression, the percentage increase in plasma B above the criterion level was significantly greater (+55%) than the corresponding percentage change in plasma F. Most patients with borderline abnormal F-DSTs (3.5 - 4.9 micrograms/dl) exhibited clearly abnormal B-DSTs (greater than 1.2 ng/ml). We conclude that the use of dexamethasone suppression of plasma B (using 1.2 ng/ml as the abnormal criterion value) is an additional indicator of an abnormal DST in depressed patients.

Plasma corticosterone and cortisol following dexamethasone in psychiatric patients.

Radioimmunoassays of cortisol (F) and corticosterone (B) were carried out in 133 plasma specimens, obtained at 0800 or 1600 h on the day following administration of dexamethasone (1.0 mg), from 69 patients admitted to a psychiatric inpatient service, to test suggestions that assays of B might complement those of F in the dexamethasone suppression test (DST) in a psychiatric setting. The overall correlation between F and B was +0.80. Concentrations of B averaged 5-8% those of F. We found close agreement (80-85%) between positive (F greater than or equal to 4.5 micrograms/dl) and negative DST results for both steroids assayed by radioimmunoassay at a criterion of greater than or equal to 1.5 ng/ml for B, as well as a reasonable compromise between sensitivity and specificity of the B-DST at that criterion. Post-dexamethasone samples obtained at 1600 h showed somewhat closer agreement between the B-DST and the F-DST than at 0800 h. Inclusion of 0800 h samples added little to the rate of positive results with the F-DST but did add to those of the B-DST by about 10% or more, depending on the criterion selected for a positive B-DST. The rate of positive DSTs among 44 patients who had both steroids assayed at both times was approximately 61%, and the agreement between positive test results among these patients was 92%. In a mixed population of acutely ill, hospitalized patients with various DSM-III diagnoses, but excluding those with medical or pharmacologic contraindications to the DST, high rates of positive DST results were obtained in patients with major depressive disorders (47-58%), with little difference found among those with bipolar, non-bipolar or melancholic characteristics. High rates also were found among manic and other acutely psychotic patients, as well as others with neurotic or characterological diagnoses, but rarely in a small group of chronic schizophrenics. Thus, a positive DST as evaluated with B or F is evidently not specific for cases of major depression, but may be indicative of acute illness, possibly with affective features. The results support suggestions that a steroid suppression test based on corticosterone may be useful to aid in diagnosis of major psychiatric illnesses and might complement or substitute for the F-DST. It may be possible to avoid certain pharmacologic complications in the DST by use of a test based on suppression of B by F rather than by dexamethasone.

Adults with attention-deficit/hyperactivity disorder: a controversial diagnosis.

The diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults has remained controversial. This paper reviews the empirical evidence to date as to whether the diagnosis of ADHD in adults is valid and consistent with the childhood syndrome. Evidence of descriptive, divergent, predictive, and concurrent validity were examined. The available literature provides evidence that adult ADHD can be reliably diagnosed and that the diagnosis confers considerable power to forecast complications and treatment response. Studies of genetic transmission, specific treatment responses, and abnormalities in brain structure and function in affected individuals are also consistent with studies in childhood ADHD. There is converging evidence that adult ADHD is a not rare, valid clinical diagnosis. In addition, studies suggest that adult and child patients with ADHD may share a similar treatment-responsive, underlying neurobiological substrate.

The naturalistic course of pharmacologic treatment of children with maniclike symptoms: a systematic chart review.

OBJECTIVE: To assess the effectiveness of mood stabilizers in treating maniclike symptoms in children. METHOD: Subjects were consecutively referred pediatric patients who, at initial intake, satisfied DSM-III-R criteria for mania on a structured diagnostic interview. We systematically reviewed their clinical records to assess (1) the course of maniclike symptoms and (2) all medications prescribed at each follow-up visit. Survival analysis was used to determine the effect of mood stabilizers and other medications on the course of maniclike symptoms. RESULTS: Of the 59 subjects meeting criteria for mania, 44 (75%) exhibited evidence of maniclike symptoms during follow-up. The occurrence of manic symptoms significantly predicted the subsequent prescription of mood stabilizers (rate ratio = 2.9, 95% confidence interval [CI] = 1.6 to 5.5), and use of mood stabilizers predicted decreases in manic symptoms (rate ratio = 4.9, 95% CI = 1.2 to 20.8). However, improvement was slow and associated with a substantial risk for relapse. CONCLUSION: Mood stabilizers were frequently used in children with maniclike symptoms, and their use was associated with significant improvement of maniclike symptoms, whereas use of antidepressant, antipsychotic, and stimulant medications was not.

Case study: adverse effects of smoking marijuana while receiving tricyclic antidepressants.

Increasingly, children and adolescents are being treated for underlying psychopathology commonly associated with the psychoactive substance use disorders. Despite this apparent increase in using medication, little is known about the interaction of drugs of abuse with the psychotropic medications. The authors describe four cases of male adolescents aged 15 to 18 years being treated with a tricyclic antidepressant for attention-deficit hyperactivity disorder who manifested transient cognitive changes, delirium, and tachycardia after smoking marijuana.

A naturalistic assessment of protriptyline for attention-deficit hyperactivity disorder.

OBJECTIVE: To evaluate the potential benefit of the tricyclic antidepressant, protriptyline, in the treatment of children and adolescents with attention-deficit hyperactivity disorder (ADHD). METHOD: All clinic patients in an outpatient pediatric psychopharmacology unit treated with protriptyline for ADHD were monitored for response to treatment. Thirteen subjects (11 male, 2 female) were treated naturalistically with protriptyline for ADHD and were administered the ADHD Symptom Rating Scale and Clinical Global Impression of Severity (CGI-S) and improvement (CGI-I) at baseline and while taking medication. All patients had failed to respond to at least one previous medication trial, and 46% had psychiatric comorbidity. RESULTS: Patients received an average protriptyline dose of 17 mg (range 5 to 30 mg) for 11.5 +/- 6.8 weeks. Of the 11 patients who continued to take protriptyline for at least 4 weeks, there was a modest reduction in the ADHD symptom checklist (p < .004) and the CGI-S (p = .032). However, using a predefined criteria of response, only 45% of patients were considered positive responders. Adverse effects were prominent, with 46% of patients reporting clinically significant problems and 38% of patients discontinuing treatment because of intolerable side effects. CONCLUSION: These findings do not support the clinical utility of protriptyline in the routine management of complex cases of ADHD in children and adolescents. However, the usefulness in noncomorbid, medication-naive ADHD individuals remains unclear.

Clinical characteristics of psychiatrically referred adolescent outpatients with substance use disorder.

OBJECTIVE: There is increasing interest in the developmental relationship of psychopathology and substance use disorders (SUD) in youths. Because the bulk of literature is focused in inpatient or incarcerated youths, inferences and generalizations are limited in outpatient settings. The clinical characteristics of psychiatrically referred outpatients were studied to determine whether differences existed in the nature and severity of comorbid psychiatric disorders when substance abuse was involved. METHOD: All diagnoses were derived from structured psychiatric interviews completed on all youths on intake assessment. Adolescents with an identified SUD (n = 38) were compared with those without SUD (n = 321) on a number of variables including past and current psychopathology, cognitive and school functioning, and overall impairment. RESULTS: Eleven percent of referred outpatients (mean age = 15.9 +/- 1.3 years) met full criteria for a SUD by parental report. Controlling for age, adolescents with SUD had higher risk for mood and disruptive behavioral disorders compared with psychiatric controls. In the majority of cases, the onset of psychopathology preceded the onset of SUD by at least 1 year. The group with SUD also had lower overall functioning and more school dysfunction and psychiatric hospitalizations than their non-SUD peers. CONCLUSIONS: Despite the small number of adolescents with SUD in this sample, these data indicate that SUD is common in outpatient psychiatry referrals. Youths with SUD appear to be at increased risk for more psychopathology and dysfunction in a number of domains.

Case study: nefazodone for juvenile mood disorders.

OBJECTIVE: Despite the increasing recognition of juvenile mood disorders, few medications have been shown to be effective. Nefazodone is a novel antidepressant that remains untested in children. Seven cases are described, including four with bipolar depression, in which nefazodone was used for depression. METHOD: The authors systematically studied the response to nefazodone used naturalistically in seven treatment-refractory and very comorbid children and adolescents (mean age +/- SD, 12.4 + 3.1) with a juvenile mood disorder that was diagnosed clinically and confirmed by structured psychiatric interview. Response to treatment was evaluated retrospectively by an independent rater using the Clinical Global Impression (CGI) of severity and improvement of depression. RESULTS: Children and adolescents received nefazodone for 13 (+/-8) weeks at a mean daily dose of 357 +/- 151 mg (3.4 mg/kg). Fifty-six percent of children and adolescents previously unresponsive to multiple medication trials manifested much to very much improvement as measured by the CGI. Two of four children with bipolar depression responded well to treatment, whereas the other two had mild manic activation. Overall, nefazodone was well tolerated, with adverse effects reported in only three subjects. CONCLUSION: Nefazodone appears to be a well-tolerated compound that may provide a treatment option for juveniles with mood disorders. Further controlled trials are warranted.

A retrospective study of serum levels and electrocardiographic effects of nortriptyline in children and adolescents.

OBJECTIVE: We retrospectively evaluated a large pediatric population treated with nortriptyline (NT) in an outpatient psychopharmacology clinic to assess pharmacokinetic and electrocardiographic (EKG) effects. METHODS: A systematic search revealed 82 children and adolescents treated naturalistically with NT. All patients with available EKGs and serum NT levels were included in the series with the exception of those receiving concomitant antipsychotic agents. Forty-three percent of subjects were receiving medications in addition to NT. RESULTS: Patients received an average (+/- SE) NT dose of 2.0 +/- 0.1 mg/kg yielding mean serum NT levels of 105.5 +/- 7.4 ng/mL. There was a linear relationship of NT dose (mg/kg) to serum NT levels (r = 0.50, p < 0.0001). NT treatment resulted in small increases in heart rate, and PR, QRS, and QTc intervals (all ps < 0.01), of similar magnitude in children and adolescents. Individuals with the highest baseline EKG indices had the least amount of change in those indices with NT treatment. There were only a few statistically significant associations between NT dose or serum NT levels and EKG parameters. NT treatment was significantly associated with the onset of asymptomatic sinus tachycardia (heart rate > 100 beats per minute), and prolongation of the EKG QRS (> 100 msec) and QTc (> 440 msec) intervals. CONCLUSIONS: These findings suggest: (1) NT has a predictable dose to level relationship, (2) the effect of NT on the EKG in this age group is mild and similar to that reported with other tricyclic antidepressants, and (3) there are few age-specific differences in NT-induced EKG changes.

Growth deficits in ADHD children revisited: evidence for disorder-associated growth delays?

OBJECTIVE: To reevaluate the hypothesis that stimulants cause growth deficits in children with attention-deficit hyperactivity disorder (ADHD). METHOD: Growth deficits in height and weight were examined in 124 children and adolescents with ADHD and 109 controls, using appropriate correction by age and parental height measures and attending to issues of pubertal stage, treatment, and psychiatric comorbidity. RESULTS: Small but significant differences in height were identified between ADHD children and controls. However, height deficits were evident in early but not late adolescent ADHD children and were unrelated to use of psychotropic medications. There was no evidence of weight deficits in ADHD children relative to controls, and no relationship between measures of malnutrition and short stature was identified. CONCLUSIONS: ADHD may be associated with temporary deficits in growth in height through mid-adolescence that may normalize by late adolescence. This effect appears to be mediated by ADHD and not its treatment.

Clonidine for sleep disturbances associated with attention-deficit hyperactivity disorder: a systematic chart review of 62 cases.

OBJECTIVE: Children and adolescents with attention-deficit hyperactivity disorder (ADHD), with or without psychostimulant treatment, frequently suffer from sleep disturbances. This report evaluates the use of clonidine in the treatment of sleep disturbances associated with ADHD. METHOD: A systematic search of a computerized database in an outpatient pediatric psychopharmacology unit of patients treated with clonidine for ADHD-associated sleep disturbances (N = 62; 42 children and 20 adolescents) was performed. Patients were rated retrospectively about the type and severity of sleep disturbances at baseline and after treatment with clonidine. RESULTS: A majority of patients (85%) treated with clonidine for ADHD-associated sleep disturbances were considered to be much to very much improved by the National Institute of Mental Health global assessment of improvement (sleep). Nighttime clonidine doses ranged from 50 to 800 micrograms (mean +/- SEM; 157 +/- 14 micrograms), and subjects received clonidine for 35.5 +/- 3.5 months. There was no association between response and age group, gender, comorbidity, or concurrent pharmacotherapy. Children and adolescents with ADHD with baseline, medicine-induced, or medicine-exacerbated sleep disturbances responded equally well to clonidine treatment. Mild adverse effects were reported in 19 subjects (31%). CONCLUSIONS: These findings suggest that clonidine may be an effective agent for sleep disturbances associated with ADHD, or its treatment, and warrant further controlled investigations.

Similarities in response to fluoxetine in the treatment of children and adolescents with obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a relatively common disorder that frequently has its onset in childhood and is associated with substantial morbidity and dysfunction despite availability of new treatments. However, antiobsessional agents have not been systematically evaluated in young children and their effectiveness beyond the short term has not been well studied. The purpose of this study was to evaluate the usefulness of fluoxetine in the long-term treatment of both children and adolescents with OCD. METHOD: All pediatric patients with a DSM-III-R diagnosis of OCD who were treated with fluoxetine were ascertained from retrospective chart reviews of a pediatric psychopharmacology clinic. Response to treatment was evaluated by experienced clinicians using the Clinical Global Impression Scale. RESULTS: Of 38 identified patients, 28 (74%) showed moderate to marked improvement of OCD symptoms on doses averaging 50 mg/day (1.0 mg/kg per day) over an average follow-up period of 19 months. Similar effects were observed in children and adolescents. CONCLUSION: Although limited by their retrospective nature, these findings indicate that fluoxetine may be effective in prepubertal children and that the effect can be sustained over time.