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To examine the safety and efficacy of fluoxetine in child and adolescent obsessive-compulsive disorder (OCD).Between 1991 and 1998, 43 patients were randomly assigned to fluoxetine or placebo for 8 weeks. Dosing was fixed for the first 6 weeks (up to 60 mg/day) and then could be increased to 80 mg/day. Responders entered an 8-week maintenance phase. The primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impression-Improvement (CGI-I) scale. Analyses were done on the intent-to-treat sample.Fluoxetine patients (n = 21) had significantly lower CY-BOCS scores than placebo patients (n = 22) after 16 (but not 8) weeks. Fluoxetine responders (n = 11) had significantly lower CY-BOCS scores than placebo responders (n = 7) after an additional 8 weeks of treatment. After 16 weeks, 57% of fluoxetine (versus 27% of placebo) patients were much or very much improved on the CGI-I scale (p.05). No patient terminated the study because of adverse medication effects.Fluoxetine was well tolerated and effective for the treatment of child and adolescent OCD, but fluoxetine's full effect took more than 8 weeks to develop.

The efficacy and tolerability of nefazodone in the treatment of major depression among Spanish-monolingual Hispanics was examined and compared to historical controls among English-speaking, predominantly non-Hispanic subjects. Fifty monolingual Hispanic outpatients with major depression and a HAM-D17 score ≥18 were treated with nefazodone in a flexible-dose 8-week open-label protocol. Sixty-three percent of the intent-to-treat (ITT) sample with ≥1 efficacy visit were considered responders according to CGI-I criteria, falling within the range of response rates (58–69%) reported in six prior nefazodone trials with non-Hispanic subjects. Significant improvement was found for the ITT and completer samples in HAM-D17, HAM-D28, and SCL-90 scores and in two measures of psychosocial functioning. Endpoint mean dose in the ITT sample was 379 mg/day (SD=170), also within the range of previous trials (321–472mg/day). Adverse effects were not elevated, with only dry mouth (8%) reported by >6% of subjects. However, 42% of the sample dropped out of treatment before study termination, usually because of side effects or due to family or work difficulties, a higher rate than previously reported for nefazodone (21–33%). This open trial finds nefazodone to be an efficacious treatment for major depression among monolingual Hispanics, with comparable efficacy to previous controlled trials among non-Hispanic subjects. Double-blind studies are required to confirm this comparable efficacy. Mean endpoint doses and adverse effect rates similar to previous trials do not support the need for reduced doses of nefazodone among Hispanics. However, an elevated rate of treatment discontinuation threatens treatment efficacy among this population. Causes for this elevated rate require explanation, given the apparently unremarkable pattern of adverse effect reports. Depression and Anxiety 13:118–124, 2001. © 2001 Wiley-Liss, Inc.

Objective: Ataque de nervios is a common, self-labeled Hispanic folk diagnosis. It typically describes episodic, dramatic outbursts of negative emotion in response to a stressor, sometimes involving destructive behavior. Dissociation and affective dysregulation during such episodes suggested a link to childhood trauma. We therefore assessed psychiatric diagnoses, history of ataque, and childhood trauma in treatment-seeking Hispanic outpatients (N = 70). Significantly more subjects with an anxiety or affective disorder plus ataque reported a history of physical abuse, sexual abuse, and/or or a substance-abusing caretaker than those with psychiatric disorder but no ataque. In some Hispanic individuals, ataque may represent a culturally sanctioned expression of extreme affect dysregulation associated with childhood trauma. Patients with ataque de nervios should receive a thorough traumatic history assessment.

We report the results of an 8-week open trial of imipramine in 15 patients with social phobia. Nine patients completed the trial; six dropped out early because of adverse effects. The mean reduction in the Liebowitz Social Anxiety Scale was 15% and 18% for the intent-to-treat and completer groups, respectively; the overall response rate (based on the Clinical Global Impression Scale of 1 or 2, very much or much improved) was 20% (3/15) and 22% (2/9), respectively. The results from this open trial do not support the efficacy of imipramine as a treatment for social phobia.

The current study assesses the relationship between presenting symptomatology of the self-labeled Hispanic popular diagnosis of ataques de nervios and the specific co-morbid psychiatric diagnoses. Hispanic subjects seeking treatment at an anxiety disorders clinic (n = 156) were assessed with a specially designed self-report instrument for both traditional ataque de nervios and panic symptoms, and with structured or semistructured psychiatric interviews for Axis-I disorders. This report focuses on 102 subjects with ataque de nervios who also met criteria for panic disorder, other anxiety disorders, or an affective disorder. Distinct ataque symptom patterns correlated with co-existing panic disorder, affective disorders, or other anxiety disorders. Individuals with both ataque and panic disorder reported the most asphyxia, fear of dying, and increased fear during their ataques. People with ataques who also met criteria for affective disorder reported the most anger, screaming, becoming aggressive, and breaking things during ataques. Ataque positive subjects with other anxiety disorders were less salient for both panic-like and emotional-anger symptoms. The findings suggest that (a) ataque de nervios is a popular label referring to several distinct patterns of loss of emotional control, (b) the type of loss of emotional control is influenced by the associated psychiatric disorder, and (c) ataque symptom patterns may be a useful clinical marker for detecting psychiatric disorders. Further study is needed to examine the relationship between ataque de nervios and psychiatric disorders, as well as the relationship to cultural, demographic, environmental, and personality factors.

The psychological and physiological effects of acute low-potency benzodiazepine administration on lactate-induced panic were examined in 10 patients with panic disorder (PD). The patients, who had panicked during a standard sodium-lactate infusion, underwent a repeat infusion modified by pretreatment with intravenous diazepam (5 mg). Acute Panic Inventory (API) scores preceding the second lactate infusion, which were associated with diazepam pretreatment, were significantly reduced in compared with those measured before the first lactate infusion. However, the second visit “fear of doom” item of the API was significantly reduced relative to the same time point of the first visit 35 min before lactate infusion, when diazepam had not yet been administered. Thus, the reduction of prelactate anxiety preceding the second infusion appeared to reflect both pharmacological and nonpharmacological contributions. The diazepam pretreatment condition was associated with a significantly increased infusion duration and a significant attenuation of rate of API symptom increase in response to lactate. Despite significant attenuation of lactate infusion effects associated with the diazepam pretreatment condition, 7 of 10 patients experienced a second panic attack. This pilot study suggests that diazepam pretreatment is associated with a marked reduction of symptomatic response during a second lactate infusion, although the magnitude of attenuation observed was insufficient to block lactate-induced panic in a majority of lactate-vulnerable PD patients.

Objective: Ataque de nervios ("attack of nerves") is an illness category used frequently by Hispanic individuals to describe one or more particular symptom complexes. A review of the literature on ataque suggested some overlap with panic disorder. This study investigated the overlap with panic disorder as well as other DSM-III-R axis I disorders. Method: Hispanic subjects seeking treatment at an anxiety disorders clinic (N = 156) were assessed with a specially designed questionnaire for self-report of ataque de nervios and panic symptoms and with structured or semistructured psychiatric interviews for axis I disorders. Results: Seventy percent of the subjects reported at least one ataque de nervios; 80% of these were female, whereas 57% of the group without these attacks were female. There were no differences in DSM-III-R diagnoses between the groups with and without ataque de nervios. Ataque was frequently associated with one or more anxiety and affective disorders, including panic disorder, generalized anxiety disorder, recurrent major depression, and anxiety not otherwise specified. Of the 45 subjects with both ataque de nervios and primary panic disorder, 80% appeared to have labeled panic disorder as ataque. Ataque de nervios was associated with panic symptoms even in subjects without panic disorder, but the self-reporting of ataque conveyed additional clinical information about the subjects with panic disorder. Ataque de nervios was similar in frequency and symptoms among subjects of Dominican and Puerto Rican origin. Conclusions: Ataque de nervios overlaps with panic disorder but is a more inclusive construct. Further study of its interrelation with axis I disorders is needed.

In a preliminary trial, five oral-clomipramine-refractory patients with obsessive-compulsive disorder (OCD) were treated openly with 14 intravenous clomipramine infusions each. Using standardized assessments, three patients were rated as much improved, one as unchanged, and one as minimally improved. Statistically significant improvements were noted on both the Yale-Brown Obsessive Compulsive Scale and the NIMH Global OCD scores. No patient discontinued treatment because of side effects. Although the results are provocative in that three of five patients were much improved at the end of the protocol, conclusions about preferential efficacy for the intravenous route must await a placebo-controlled trial.

We sought to determine whether adults with obsessive-compulsive disorder (OCD) who respond to intensive exposure and response (ritual) prevention (EX/RP) with or without clomipramine (CMI) fare better 12 weeks after treatment discontinuation than responders receiving CMI alone. After receiving 12 weeks of treatment (EX/RP, CMI, EX/RP+CMI, or pill placebo [PBO] in a randomized clinical trial conducted at three outpatient research centers), 46 adults with OCD who responded to treatment (18 EX/RP, 11 CMI, 15 EX/RP+CMI, 2 PBO) were followed after treatment discontinuation for 12 weeks. Patients were assessed every 4 weeks with the Yale-Brown Obsessive-Compulsive Scale, the National Institutes of Health Global Obsessive-Compulsive Scale, and the Clinical Global Impressions scale by an evaluator who was blind to original treatment assignment. The primary hypothesis was that EX/RP and EX/RP+CMI responders would be less likely to relapse 12 weeks after treatment discontinuation than responders to CMI alone. Twelve weeks after treatment discontinuation, EX/RP and EX/RP+CMI responders, compared to CMI responders, had a significantly lower relapse rate (4/33 = 12% versus 5/11 = 45%) and a significantly longer time to relapse. The CMI relapse rate was lower than previously reported. Nonetheless, responders receiving intensive EX/RP with or without CMI fared significantly better 12 weeks after treatment discontinuation than responders receiving CMI alone.

Objective: We sought to determine optimal cutoff values for the Liebowitz Social Anxiety Scale (LSAS) total and subscale scores for the diagnosis of social anxiety disorder (SAD) and designation of the generalized subtype of SAD. Method: Three hundred and sixty-four patients from a multi-site sample who met criteria for SAD according to structured diagnostic interview, 262 of whom met criteria for the generalized subtype, and 34 control participants free of current Axis I disorders participated in this study. All participants were given the Liebowitz Social Anxiety Scale by an independent assessor. Results: Receiver Operating Characteristics analysis revealed that the LSAS performed well in identifying individuals who met criteria for SAD and for the generalized subtype of SAD. Cutoffs of 30 for SAD and 60 for its generalized subtype on the LSAS total score represented the best balance of specificity and sensitivity. Conclusions: These findings provide support for the use of the Liebowitz Social Anxiety Scale for the identification of individuals with SAD and its generalized subtype in clinical settings. Identification of patients with SAD should increase the percentage of these patients who receive appropriate treatment for this impairing disorder.

Uncontrolled reports suggest that intravenous clomipramine hydrochloride may be effective for patients with obsessive-compulsive disorder (OCD) who are nonresponsive to oral clomipramine.Fifty-four patients with oral clomipramine-refractory OCD were randomized to receive 14 infusions of either placebo or clomipramine hydrochloride, starting at 25 mg/d and increasing to 250 mg/d. Ratings were conducted double-blind after infusion 14 among 54 patients, single-blind 1 week later among 39 patients, and nonblind 1 month later among 31 patients. Response was based on a Clinical Global Impressions rating of at least "much improved."Six (21%) of 29 patients randomized to receive intravenous (i.v.) clomipramine vs 0 of 25 patients given i.v. placebo were responders after 14 infusions (df = 1, P.02). Dimensional ratings after infusion 14 revealed significant (P = .007) improvement on the National Institute of Mental Health-Obsessive-Compulsive Scale and the Clinical Global Impressions Scale (P = .03), but not the Yale-Brown Obsessive Compulsive Scale. One week later, all dimensional measures of OCD showed significant improvement. At 1 week post-i.v., 9 (43%) of 21 patients initially randomized to i.v. clomipramine and treated subsequently with oral clomipramine were responders, whereas 0 of 18 patients initially randomized to receive i.v. placebo and treated subsequently with several days of open-label i.v. clomipramine responded (df = 1, P.002). Of the 31 patients assessed 1 month after i.v. infusion (treatment not controlled), 18 (58.1%) were responders. Intravenous clomipramine treatment was safe with no serious adverse consequences.Intravenous clomipramine is more effective than i.v. placebo for patients with OCD with a history of inadequate response or intolerance to oral clomipramine. Further study of this promising treatment for refractory OCD is needed.

Recent evidence now suggests that OCD is much more common in young people than previously thought, affecting up to 200,000 children and adolescents in the United States alone. Unlike many childhood disorders, OCD appears remarkably similar for children and adults in terms of both clinical presentations and treatment response. The treatments of choice for OCD are antidepressants with potent serotonergic reuptake blocking effects such as fluoxetine and clomipramine. Both medications appear to be equally effective in terms of symptom remission, with different investigators reporting response rates in the range of 50% to 75%. Recent evidence suggests, however, that fluoxetine may be tolerated more easily than clomipramine and may be associated with less relapse upon discontinuation. Behavior therapy, either alone or in combination with medication, has been shown to be an effective alternative treatment. In spite of the increasing recognition of the disorder in both adults and children, only a handful of treatment outcome studies of child and adolescent OCD have been conducted and much work remains to be done in this area.

To assess the role of noradrenergic stimulation during lactate-induced panic, ten patients with panic disorder who panicked during a standard sodium-lactate infusion underwent a repeat infusion following intravenous clonidine pretreatment. Although clonidine significantly lowered prelactate systolic blood pressure, the drug did not significantly lower prelactate anxiety levels, as reflected by the Acute Panic Inventory (API). Clonidine blocked lactate-induced panic in four of ten subjects, a significant effect. Clonidine treatment also significantly attenuated lactate-panic symptoms, as reflected by time to panic and API comparison between trials. Nevertheless, over half the subjects still panicked in response to lactate despite clonidine. This preliminary study suggests that reduction of central noradrenergic activity by clonidine, at least at the dosage levels employed in the current study, only partially attenuates panic response to lactate. Noradrenergic theories of panic may not therefore fully account for lactate panicogenesis.

Some forms of anxiety and affective disorder, such as panic disorder and major depression, appear distinct, while other forms, such as generalized anxiety disorder and chronic depression or dysthymia, may lie on a continuum and blend with each other. However, even panic disorder and major depression have many common features. Moreover, for reasons not yet clear, they occur together frequently, and their combined occurrence in the same patient has been associated with greater severity and chronicity, decreased treatment responsiveness, and, possibly, increased familial prevalence of anxiety and/or depression. Finally, studies of primary care patients suggest the frequent occurrence of a mixed anxiety-depressive disorder that may often be subsyndromal by DSM-III-R criteria but is nevertheless associated with prominent distress and/or impairment.

Twenty-five patients with a primary DSM-III-R diagnosis of panic disorder with or without agoraphobia were treated openly with the serotonin uptake inhibitor fluoxetine for up to 12 months. For most patients, treatment was initiated at 5 mg/day to minimize adverse effects previously reported with initiation at higher doses. Nineteen (76%) experienced moderate to marked improvement in panic attacks. Four (16%) were unable to tolerate fluoxetine due to adverse effects. Initiating treatment of panic disorder with low doses of fluoxetine may increase its acceptability and permit more patients to benefit from fluoxetine.

We evaluated the role of plasma cortisol levels in determining sodium lactate-induced panic by reporting psychological, physiological, and biochemical data collected from an extended sample of 214 subjects during the "placebo" infusion (isotonic saline solution) immediately preceding the lactate infusion procedure.One hundred seventy patients with panic disorder, 101 (59%) of whom were assessed to have panicked (P group), and 69 (41%) who were assessed not to have panicked (NP group) with lactate infusion; and 44 normal healthy volunteer controls (1 of whom panicked with lactate infusion) were studied.Before the lactate infusion, the P group exhibited hypothalamic-pituitary-adrenal (HPA) axis activation (high plasma cortisol levels) and evidence of hyperventilation (low PCO2 levels) in comparison with NP and control groups. Self-reported fear, dyspnea, and diastolic blood pressure were highest in the P group, intermediate in the NP group, and lowest in the control group. Within the P group, baseline fear scores correlated inversely with PCO2 levels and positively with cortisol levels while PCO2 levels correlated negatively with cortisol levels. Significant predictors of lactate-induced panic were prelactate infusion fear and the interaction of high cortisol levels and low PCO2 levels.Combined data suggest that synchronized elevations of HPA axis activity, self-reported fear, and hyperventilation during the period before lactate infusion predisposes to lactate-induced panic.

Seventy-four patients who met DSM-III criteria for social phobia completed 8 weeks of double-blind, randomly assigned treatment with the monoamine oxidase inhibitor phenelzine sulfate, the cardioselective beta-adrenergic blocker atenolol, or placebo. The overall response rates were 64% for phenelzine, 30% for atenolol, and 23% for placebo. Phenelzine was widely superior to both atenolol and placebo on independent rater analyses and, to a lesser extent, on self-report, with no significant differences between atenolol and placebo. At the end of 16 weeks, phenelzine was still significantly superior to placebo, while atenolol showed an intermediate response that did not differ significantly from either of the other treatments. Patients with generalized social phobia constituted 76% of the sample, and they were preferentially responsive to phenelzine. The small size of the discrete social phobic sample precluded separate outcome analyses for this subtype. Overall, the findings support the responsivity of social phobia to monoamine oxidase inhibitors.

Lactate infusions produced panic attacks in one of 15 patients with social phobia, four of nine with agoraphobia, and 10 of 20 with panic disorder in a blind study. The proportion of patients with social phobia who panicked in response to lactate was significantly lower than that of patients with agoraphobia or panic disorder. These findings lend validity to the DSM-III classification of anxiety states. They also suggest that the pathophysiology of social phobia differs from that of disorders characterized by spontaneous panic attacks.

To examine the biochemical effects of 10-30 mg/day L-deprenyl, measurement of 24-hr urinary output of phenylethylamine (PEA), 3-methoxy 4-hydroxy phenylethyleneglycol (MHPG), and L-deprenyl's amphetamine metabolites were carried out before and during the treatment of atypical depressives. Platelet monoamine oxidase (MAO) activity was also assessed. With L-deprenyl 10-30 mg/day, the expected MAO B inhibition occurred, as indicated by significant increase in urinary PEA excretion and virtual disappearance of platelet MAO activity. Twenty-five to 33% of the daily dose of L-deprenyl was recovered as urinary methamphetamine or amphetamine. Excretion of MHPG was significantly decreased with L-deprenyl 10-20 mg/day. Overall, the results suggest that L-deprenyl's antidepressant effects are mediated by some mechanism other than, or in addition to, MAO B inhibition.

Preliminary reports have indicated that platelet monoamine oxidase (MAO) activity is elevated in patients with anxiety disorder. We compared MAO activity in 20 drug-free patients with panic disorder with 20 age- and sex-matched normal controls. MAO activity in patients was significantly higher than in normals. MAO activity was not correlated with age or plasma catecholamine levels. The authors speculate about the possible significance of elevated MAO activity in patients with panic disorder.

Panic attacks followed sodium lactate infusions in one of seven patients with obsessive-compulsive disorder and 26 of 48 patients with panic disorder or agoraphobia with panic attacks. This suggests that lactate-induced panic is specific to the latter groups.

At low doses (e.g. 10 mg/day), L-deprenyl is thought to selectively inhibit the B isoenzyme of monoamine oxidase (MAO). The biochemical effects of L-deprenyl in depressed patients have, however, received little detailed study. It is unclear if L-deprenyl maintains MAO specificity when chronically administered in effective antidepressant dosages. Also, L-deprenyl has pharmacological effects other than MAO inhibition, such as blockade of norepinephrine (NE), reuptake (Knoll, 1976), inhibition of NE release (Knoll, 1976) and metabolism to methamphetamine and amphetamine (Reynolds et al., 1978).

Sodium lactate precipitates panic in 70–100% of clinically ill patients with panic disorders. The lactate vulnerability of remitted patients is unknown. In this study, 13 panic patients completed three sequential sodium lactate infussion: one before treatment, a second when panic free on tricyclic antidepressants (TCA), and a third when in remission and unmedicated for 1 to 6 months. Three out of 13 patients panicked at the third infusion as compared to 0/13 infused on TCA and 7/12 at pretreatment infusion. This result (1) indicates that lactate vulnerability can exist in clinically well, unmedicated patients, and (2) raises the possibility that lactate vulnerability may be a trait characteristic. Further studies are needed before definite conclusions can be drawn.

The intensity needed to detect dichotic click stimuli was measured in 14 bipolar depressed patients, 19 unipolar depressed patients, and 15 normal controls. The results replicated, in unmedicated bipolar depressed patients, an earlier finding of reversed lateral asymmetry in medicated affective psychotic patients. Two new findings concern the relation of lateral asymmetry patterns to diagnostic subtypes of the Research Diagnostic Criteria and symptom ratings on the Schedule for Affective Disorders and Schizophrenia. First, patients with bipolar disorders (history of mania or hypomania) were more likely than patients with unipolar disorders to display reversed lateral asymmetry. Second, greater severity of depressive or endogenous symptoms was associated with less lateral asymmetry.

We investigated the antidepressant efficacy of l-deprenyl (selegiline), a selective monoamine oxidase B inhibitor (MAOI), in a six-week open trial of 17 patients with atypical depression. Such patients have previously been shown to benefit from nonselective MAOIs such as phenelzine sulfate. Ten patients (59%) responded to l-deprenyl, but nine required dosages above the 10 to 20 mg/day used in previous investigations. l-Deprenyl was superior to six weeks of placebo administered to diagnostically similar patients in a separate double-blind study. In contrast with previous findings with pheneizine, responders to l-deprenyl differed from nonresponders by having lower baseline anxiety ratings. Even at high dosages, there appeared to be fewer side effects with l-deprenyl than with nonselective MAOIs.

• To assess the pharmacologic and phenomenologic comparability of lactate-induced and naturally occurring panic attacks, patients meeting DSM-III criteria for panic disorder or agoraphobia with panic attacks were infused with 0.5M racemic sodium lactate before and after successful drug treatment. Lactate-induced and naturally occurring panic attacks were symptomatically similar. Following treatment, the patients' response to lactate did not differ from that of normal controls, whereas the pretreatment panic rate was much higher. These data suggest that lactate acts, by as yet unidentified mechanisms, to trigger the same panic attacks as occur spontaneously in vulnerable persons.

• Thirty-one of 43 patients with panic disorder or agoraphobia with panic attacks and none of 20 normal controls panicked in response to infusions of sodium lactate. Before receiving lactate, patients showed higher heart rates than controls and also signs of hyperventilation. During lactate infusion, patients who did not panic, nevertheless, developed higher lactate and pyruvate levels and greater ionized calcium and pH changes than controls. Lactate-induced panic attacks were regularly accompanied by biological changes consistent with hyperventilation and central noradrenergic activation and irregularly by elevation of plasma norepinephrine and cortisol levels. Panic attacks were not associated with changes in epinephrine or calcium levels or pH. Baseline arousal increased the likelihood of panic during lactate infusion. It is hypothesized that lactate-induced panic primarily involves central noradrenergic discharge with inconsistent peripheral manifestations.

Many clinical and theoretic attempts have been made to link anxiety disorders and the beta-adrenergic nervous system. Six patients with panic disorder, who had panic attacks produced by sodium lactate infusions, were given repeated lactate infusions that were immediately preceded by intravenous administration of propranolol hydrochloride. In all cases, propranolol pretreatment infusion failed to prevent panic attacks, anxiety, tachycardia, and increased systolic BP during the lactate infusion.

Fluoxetine is a new antidepressant with pharmacologic effects apparently limited to blockade of neuronal serotonin reuptake. We entered 20 patients who met DSM-III criteria for either panic disorder or agoraphobia with panic attacks into an open, uncontrolled pilot study of fluoxetine. Four responded to placebo in the week before fluoxetine administration and were dropped from the study. Of the remaining 16 patients, nine were nonresponders and seven were responders, with complete cessation of their panic attacks. Eight of the nine nonresponders were unable to tolerate the side effects of fluoxetine. In contrast, all of the responders (and one nonresponder) experienced minimal side effects. Fluoxetine may be effective in the treatment of panic attacks, perhaps implicating the serotonergic system in the pathophysiology of panic disorder. Future studies should use very low doses of fluoxetine to initiate treatment.

• First-degree (N = 195) and second-degree (N = 785) adult relatives of prepubertal children with major depression (N = 48), children with nonaffective psychiatric disorders (N = 20), and normal children (N = 27) were assessed by the Family History—Research Diagnostic Criteria method (FH-RDC), except for the adult informant (usually the mother), who was directly interviewed. Compared with normal controls, prepubertal children with major depressive disorder (MDD) had significantly higher familial rates of psychiatric disorders in both first- and second-degree relatives, especially MDD, alcoholism, and "other" (mostly anxiety) diagnoses. Relatives of children in the nonaffective psychiatric control (PC) group had low rates of alcoholism, high rates of other (anxiety) disorder diagnoses, and intermediate rates of MDD (accounted for by those children with separation anxiety). This suggests that prepubertal onset of major depression may be especially likely in families with a high aggregation of affective disorders when these families also have a high prevalence of alcoholism, and that a proportion of children without affective disorder but with separation anxiety disorder in this study were at high risk for the development of affective illness later in life. These results support the validity of prepubertal-onset depressive illness as a diagnostic category, and are consistent with high familial rates of MDD and other psychiatric disorders found in family studies of adolescent and early-onset adult probands with major affective disorders, and with studies of the offspring of parents with major affective disorders. Within the child MDD group substantial heterogeneity was found. Low familial rates of MDD were associated with suicidality and comorbid conduct disorder in the child probands. The highest familial rates of MDD, approximately threefold those in the normal controls, and all the bipolar relatives, were found in the families of prepubertal probands with MDD who never had a concrete suicidal plan or act and who were without comorbid conduct disorder. A useful nosological continuum in which to classify prepubertal MDD may be to place at one end those patients with comorbid conduct disorder and at the other end those patients with manifestations related to bipolarity, including hypomania, mania, and psychotic subtype.

The selective serotonin reuptake blocker fluoxetine was administered to 49 patients with obsessive-compulsive disorder in a 12-week open clinical trial. A minimum adequate trial of at least 8 weeks of treatment was completed by 39 patients. Response rates were 62% (24/39) of adequately treated patients and 49% (24/49) of the whole sample. These uncontrolled findings suggest that fluoxetine is of significant benefit for a substantial proportion of obsessive-compulsive disorder patients. However, controlled trials comparing fluoxetine with placebo and other active agents are needed to confirm this, as are studies aimed to delineate fluoxetine's full dose range, optimal length of treatment and relapse rate following discontinuation.