LIST REFERENCES LIST REFERENCES A) ABSTRACT ONLINE 2690364 E) OBSESSIVE-COMPULSIV... 2431 B) 1990...91 560767 F) *SUM DE 2432 C) 1985...91 2277087 G) OBSESSIVE-COMPUL.../DT 492 D) OBSESSIVECOMPULSIVE 1 H) *ON A&C&G 159 *** *** *****AMERICAN JOURNAL OF PSYCHIATRY***** (REFERENCE 1 OF 55) 91353778 Hoehn-Saric R Pearlson GD Harris GJ Machlin SR Camargo EE Effects of fluoxetine on regional cerebral blood flow in obsessive- compulsive patients. Am J Psychiatry 1991 Sep;148(9):1243-5 Six drug-free obsessive-compulsive patients were given single photon emission computerized tomography scans before and during treatment with fluoxetine. The treatment significantly reduced the patients' "hyperfrontality," as determined by the ratio between medial-frontal and whole cerebral cortex blood flow, and significantly lowered ratings of obsessive-compulsive and anxiety symptoms. Institutional address: Department of Psychiatry Johns Hopkins Hospital Baltimore MD 21205. (REFERENCE 2 OF 55) 91083114 Pato MT Pigott TA Hill JL Grover GN Bernstein S Murphy DL Controlled comparison of buspirone and clomipramine in obsessive- compulsive disorder. Am J Psychiatry 1991 Jan;148(1):127-9 Eighteen outpatients with obsessive-compulsive disorder were treated with either buspirone, a partial serotonin agonist, or clomipramine, a serotonin uptake inhibitor, in a double-blind, random-assignment study. Both drugs led to statistically significant and similar improvements in scores on the Yale-Brown Obsessive-Compulsive Rating Scale and other obsessive-compulsive and depression scales. This preliminary result warrants further exploration with a larger sample and other serotonergic agents. Institutional address: Laboratory of Clinical Science NIMH NIH Bethesda Md. (REFERENCE 3 OF 55) 88338800 Jenike MA Baer L An open trial of buspirone in obsessive-compulsive disorder. Am J Psychiatry 1988 Oct;145(10):1285-6 Of 14 patients with obsessive-compulsive disorder who entered an 8- week open trial of buspirone, none improved. The ineffectiveness of buspirone may shed light on the serotonergic hypothesis that has been proposed for this disorder. Institutional address: Harvard Medical School Obsessive Compulsive Disorders Clinic and Research Unit Massachusetts General Hospital Boston 02114. (REFERENCE 4 OF 55) 87268186 Price LH Goodman WK Charney DS Rasmussen SA Heninger GR Treatment of severe obsessive-compulsive disorder with fluvoxamine. Am J Psychiatry 1987 Aug;144(8):1059-61 Ten obsessive-compulsive patients received single-blind treatment with fluvoxamine, a selective serotonin reuptake inhibitor, for several weeks following at least 2 weeks of placebo. The group showed significant improvement, as measured by several clinical scales and self-ratings; six patients were judged responders. Fluvoxamine appears effective in treating severe obsessive-compulsive disorder. (REFERENCE 5 OF 55) 85172289 Mavissakalian M Turner SM Michelson L Jacob R Tricyclic antidepressants in obsessive-compulsive disorder: antiobsessional or antidepressant agents? II. Am J Psychiatry 1985 May;142(5):572-6 The authors explored the relationship between the antiobsessional and antidepressant effects of tricyclic drugs in primary obsessive- compulsive disorders. Study 1 consisted of a controlled 12-week trial with clomipramine (N = 7) and placebo (N = 5); study 2 analyzed the pooled data from 15 patients uniformly selected and treated with either clomipramine or imipramine. Although the antiobsessional and antidepressant effects of the drugs covaried, their antidepressant action was not a prerequisite for their antiobsessional effect. The findings suggest that clomipramine and probably imipramine possess specific antiobsessive effects that are at least partially independent of their antidepressant effects. *****ARCHIVES OF GENERAL PSYCHIATRY***** (REFERENCE 6 OF 55) 91024497 Pigott TA Pato MT Bernstein SE Grover GN Hill JL Tolliver TJ Murphy DL Controlled comparisons of clomipramine and fluoxetine in the treatment of obsessive-compulsive disorder. Behavioral and biological results. Arch Gen Psychiatry 1990 Oct;47(10):926-32 Treatment with fluoxetine hydrochloride was compared with treatment with clomipramine hydrochloride in two groups of patients with obsessive-compulsive disorder using two different experimental designs. In the first group of 11 patients with obsessive-compulsive disorder studied using a randomized, double-blind, crossover design, treatment with fluoxetine for 10 weeks was found to produce therapeutic effects similar to treatment with clomipramine for 10 weeks. There were significantly fewer total side effects reported during fluoxetine than clomipramine treatment. Drug tapering and placebo substitution in the 4-week crossover interval phase led to substantial relapses in obsessive-compulsive disorder symptoms and depression. Furthermore, responses to the second drug took as long to occur as responses to the first drug, although both drugs are thought to act by a common mechanism, serotonin uptake inhibition. A second group of 21 patients with obsessive-compulsive disorder that had been previously stabilized on clomipramine treatment with at least partial benefit were crossed over to fluoxetine treatment in a double-blind fashion. After 10 weeks of fluoxetine administration, most patients manifested behavioral rating scores of obsessive-compulsive disorder and depressive symptoms that were comparable with precrossover ratings completed during clomipramine treatment. A significant exacerbation in obsessive-compulsive disorder and depression ratings as well as a similar lag in therapeutic efficacy were also noted in this second cohort of patients with obsessive-compulsive disorder. Platelet 5-HT concentrations were reduced 95% during both clomipramine and fluoxetine treatment periods. These results suggest that fluoxetine may represent a viable alternative to clomipramine in the treatment of obsessive-compulsive disorder, although further studies with larger sample sizes are needed. Institutional address: Laboratory of Clinical Science National Institute of Mental Health National Institutes of Health Clinical Center Bethesda MD 20892. (REFERENCE 7 OF 55) 90365596 Benkelfat C Nordahl TE Semple WE King AC Murphy DL Cohen RM Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Patients treated with clomipramine. Arch Gen Psychiatry 1990 Sep;47(9):840-8 In a recent study, we reported abnormal local cerebral glucose metabolic rates in the orbital frontal cortex of patients with obsessive-compulsive disorder. Eight patients with obsessive- compulsive disorder scanned previously were scanned again during treatment with the tricyclic antidepressant clomipramine hydrochloride. Comparisons of local cerebral glucose metabolic rates for both groups showed a relative decrease in regions of the orbital frontal cortex and the left caudate, and an increase in other areas of the basal ganglia, including the right anterior putamen. When comparing patients who responded well to clomipramine with those who were either poor or partial responders, we found significant decreases only in the left caudate of patients who responded well to the drug. The present study suggests that clomipramine-induced improvement in obsessive-compulsive symptoms is associated with a return of regional brain metabolism to a more normal level in regions of the orbital frontal cortex and the caudate nucleus. Institutional address: Section on Clinical Neuropharmacology National Institute of Mental Health Bethesda Md. (REFERENCE 8 OF 55) 89087238 Benkelfat C Murphy DL Zohar J Hill JL Grover G Insel TR Clomipramine in obsessive-compulsive disorder. Further evidence for a serotonergic mechanism of action. Arch Gen Psychiatry 1989 Jan;46(1):23-8 Data from several previous studies link clomipramine's potent serotonergic effects to its clinical efficacy in reducing the symptoms of obsessive-compulsive disorder (OCD). To investigate this relationship further, we administered the serotonin (5-HT) receptor antagonist, metergoline, and placebo to ten patients with OCD in a crossover study carried out under double-blind, random-assignment conditions. In a previous study of untreated patients with OCD, we found no differences in the behavioral response to single-dose administration of metergoline or placebo. In the present study, patients with OCD receiving clomipramine hydrochloride on a long-term basis (with an average 40% lessening in OC symptoms) responded to a four-day period of administration of metergoline with significantly greater self- and observer-rated anxiety compared with the four-day placebo period. Obsessive-compulsive symptoms also tended to be greater during the metergoline phase, with significant drug-time interactions for both OC symptoms and anxiety peaking on day 4 of the metergoline phase. As anticipated, metergoline lowered plasma prolactin concentrations (providing evidence of physiologically significant 5-HT antagonism) but did not alter plasma clomipramine concentrations. These data further support the hypothesis that clomipramine's therapeutic behavioral effects in OCD are mediated via serotonergic mechanisms. Institutional address: Section on Clinical Neuropharmacology National Institute of Mental Health Bethesda MD 20892. (REFERENCE 9 OF 55) 88105856 Zohar J Insel TR Zohar-Kadouch RC Hill JL Murphy DL Serotonergic responsivity in obsessive-compulsive disorder. Effects of chronic clomipramine treatment. Arch Gen Psychiatry 1988 Feb;45(2):167-72 Clomipramine is a potent serotonin reuptake blocker that decreases the symptoms of obsessive-compulsive disorder (OCD). To investigate whether clomipramine treatment in OCD affects brain serotonergic responsiveness, metachlorophenylpiperazine (mCPP), a selective serotonin agonist, and placebo were given under double-blind conditions to nine patients with OCD before and after treatment with clomipramine. Unlike our previous observations of a marked transient increase in obsessional symptoms and anxiety following 0.5 mg/kg of mCPP, readministration of mCPP after four months of treatment with clomipramine did not significantly increase obsessional symptoms and anxiety. Similarly, the hyperthermic effect of mCPP observed before treatment was eliminated after treatment with clomipramine. These findings are consistent with the development of adaptive subsensitivity to the serotonergic agonist mCPP during clomipramine treatment. A similar alteration in the response to endogenous serotonin may mediate clomipramine's antiobsessional effects. Institutional address: Laboratory of Clinical Science National Institute of Mental Health Bethesda Md. *****JOURNAL OF CLINICAL PSYCHIATRY***** (REFERENCE 10 OF 55) 91267974 Lydiard RB Coexisting depression and anxiety: special diagnostic and treatment issues. J Clin Psychiatry 1991 Jun;52 Suppl:48-54 Anxiety and depression often coexist in the clinical setting. Using panic disorder as an example, the author presents an overview of the prevalence, familial aspects, and long- and short-term outcomes of such comorbid disorders. Evidence regarding the diagnostic category of mixed anxiety-depression is also reviewed. On the basis of the limited available data, the author advances possible treatment strategies for treating patients with comorbid depression and anxiety disorders. Combined pharmacologic therapies may be indicated to optimize treatment for some patients. The review underscores the need for treatment studies in patients with depression and coexisting anxiety. Institutional address: Institute of Psychiatry Medical University of South Carolina Charleston 29425. (REFERENCE 11 OF 55) 91236682 Opler LA Feinberg SS The role of pimozide in clinical psychiatry: a review. J Clin Psychiatry 1991 May;52(5):221-33 Pimozide, a diphenylbutylpiperidine neuroleptic which is FDA-approved as a backup treatment for Gilles de la Tourette's syndrome, has been used abroad for many years as a treatment of schizophrenia and has been recently reported to be particularly effective in treating monosymptomatic hypochondriacal psychosis and delusional jealousy. Pimozide may also have a role in the treatment of negative schizophrenic symptoms, pain syndromes, and obsessive compulsive disorder. After reviewing the relevant clinical literature supporting these indications, the authors review preclinical studies that provide points of departure regarding biochemical mechanisms underlying this unique therapeutic profile. Institutional address: Department of Psychiatry College of Physicians & Surgeons Columbia University New York N.Y. (REFERENCE 12 OF 55) 91231457 Schatzberg AF Dosing strategies for antidepressant agents. J Clin Psychiatry 1991 May;52 Suppl:14-20 In this paper, the author reviews the dosing strategy for each major class of antidepressant drugs. The long-accepted strategy of moving from low to high dosages may need to be revised when the newer serotonergic agents are used to treat depressed patients. Evidence indicates that these drugs may be both better tolerated and more effective at lower dosages. Several studies in support of this hypothesis are reviewed. Possible dosing strategies of serotonergic agents, such as fluoxetine, in the treatment of obsessive compulsive disorder, obesity, and other nondepressive disorders, are also discussed. Institutional address: Department of Psychiatry Harvard Medical School Boston Mass. (REFERENCE 13 OF 55) 91170180 Hoehn-Saric R Harris GJ Pearlson GD Cox CS Machlin SR Camargo EE A fluoxetine-induced frontal lobe syndrome in an obsessive compulsive patient. J Clin Psychiatry 1991 Mar;52(3):131-3 The authors report the occurrence of apathy, indifference, inattention, and perseveration in an obsessive compulsive patient taking high doses of fluoxetine. These changes were associated with a decrease in cerebral blood flow in the frontal lobes and changes in neuropsychological tests generally associated with frontal lobe impairment. These clinical manifestations disappeared 4 weeks after discontinuation of fluoxetine. Institutional address: Johns Hopkins Medical Institutions Department of Psychiatry and Behavioral Sciences Baltimore MD 21205. (REFERENCE 14 OF 55) 91107598 Jenike MA Baer L Buttolph L Buspirone augmentation of fluoxetine in patients with obsessive compulsive disorder. J Clin Psychiatry 1991 Jan;52(1):13-4 Twenty patients with obsessive compulsive disorder were treated openly with fluoxetine for 20 weeks. In 10 of the patients, addition of buspirone during the last 8 weeks improved clinical response. The role of augmenting strategies is discussed. Institutional address: Harvard Medical School Boston Mass. (REFERENCE 15 OF 55) 91079130 Fallon BA Liebowitz MR Hollander E Schneier FR Campeas RB Fairbanks J Papp LA Hatterer JA Sandberg D The pharmacotherapy of moral or religious scrupulosity. J Clin Psychiatry 1990 Dec;51(12):517-21 Moral or religious scrupulosity is a disabling condition which is sometimes seen in patients with obsessive compulsive disorder (OCD). The authors described 10 patients with moral or religious scrupulosity who were treated with fluoxetine or clomipramine. Seven of the 10 patients completed open treatment of at least 8 weeks without requiring adjunctive medication; 5 of those 7 patients were rated as much improved. Among the 3 patients who required adjunctive medication, 1 was rated as much improved. Of the 4 nonresponders at 3 months, 2 responded after longer treatment trials. These results suggest that extreme moral or religious concerns and behaviors might be a form of OCD and that the scrupulosity can be effectively treated with serotonin reuptake blockers. Institutional address: NYS Psychiatric Institute NY 10032. (REFERENCE 16 OF 55) 91009054 Insel TR New pharmacologic approaches to obsessive compulsive disorder. J Clin Psychiatry 1990 Oct;51 Suppl:47-51; discussion 56-8 Although obsessive compulsive disorder (OCD) traditionally has been considered a treatment-refractory syndrome, rigorous treatment studies over the past decade have demonstrated that most OCD patients respond to specific behavioral or pharmacologic therapies. In terms of the pharmacologic treatment of OCD, a relatively small group of antidepressant drugs (clomipramine, fluvoxamine, and fluoxetine) have been demonstrated to be antiobsessional. Several related antidepressants (desipramine, nortriptyline) appear to be ineffective for OCD. Clinical response requires prolonged treatment (greater than 6 weeks) with antiobsessional drugs and efficacy is not limited to depressed OCD patients. The few drugs that have been demonstrated to be antiobsessional share a high potency for the blockade of serotonin reuptake, suggesting a serotonergic mechanism for antiobsessional drug action. This suggestion has been further strengthened by studies demonstrating a high correlation between clinical response and changes in serotonergic markers with clomipramine treatment. Moreover, a serotonin antagonist, metergoline, appears to partly reverse the improvement observed following chronic clomipramine treatment. Overall, only about 50% of OCD patients appear to respond in any given pharmacologic treatment trial. Adjunctive treatments, such as lithium or L-tryptophan, have been reported to help in some cases. In addition, the use of neuroleptics either alone or in combination with antiobsessional drugs may be useful for OCD patients with psychotic features or tics. Pharmacologic treatments should be considered only one element of the therapeutic approach to be integrated with behavioral techniques as well as psychosocial interventions for the relief of this very intriguing syndrome. Institutional address: Laboratory of Clinical Science National Institute of Mental Health Poolesville Md. 20837. (REFERENCE 17 OF 55) 90337931 Greist JH Treatment of obsessive compulsive disorder: psychotherapies, drugs, and other somatic treatment. J Clin Psychiatry 1990 Aug;51 Suppl:44-50; discussion 55-8 Ninety percent of obsessive compulsive patients can be helped by treatment with behavior therapy and drug treatment, used sequentially or concurrently. The effectiveness of these treatments has been demonstrated in controlled clinical trials and is superior to electroconvulsive therapy and dynamic or cognitive psychotherapies for this disorder. Potent serotonin uptake inhibiting drugs, from the class of heterocyclic antidepressants, are the most effective antiobsessional medications currently available. Although these drugs usually do not induce complete remission, they can reduce obsessive compulsive symptoms by 30% to 42%. Behavior therapy combines exposure and response prevention, which the patient first learns with the therapist and then practices independently. With behavior therapy, patients confront the triggers for their anxiety and then delay, diminish, or discontinue their rituals. Reduction in symptoms with behavior therapy averages 50% or greater. Behavior therapy is usually not effective in patients who are substantially depressed, are delusional, fail to comply, or undermine therapy with covert rituals or avoidance techniques. The rare patient with very severe obsessive compulsive disorder who does not respond to behavior or drug therapy may be a candidate for psychosurgery. Modern psychosurgical procedures are quite safe and can improve symptoms in the majority of otherwise unresponsive patients. Institutional address: Department of Psychiatry University of Wisconsin Madison. (REFERENCE 18 OF 55) 90216657 Murphy DL Pigott TA A comparative examination of a role for serotonin in obsessive compulsive disorder, panic disorder, and anxiety. J Clin Psychiatry 1990 Apr;51 Suppl:53-8; discussion 59-60 Recent clinical and laboratory studies have suggested that changes in brain serotonin (5-HT) function may contribute to anxiety symptoms and anxiety-type behaviors. Among the anxiety disorders, perhaps the most compelling evidence implicating 5-HT exists for obsessive compulsive disorder (OCD). In controlled trials, patients with OCD were markedly more responsive to treatment with 5-HT-selective uptake inhibitors such as clomipramine, fluvoxamine, or fluoxetine than to norepinephrine-selective or nonselective uptake inhibitors or to other psychoactive drugs. Studies with 5-HT agonists and antagonists also support a role for 5-HT in OCD. In this review, pharmacologic studies involving 5-HT-selective therapeutic and anxiogenic agents and non-5-HT-selective anxiogenic agents in patients with OCD are compared and contrasted with similar studies in patients with anxiety and panic disorder. Institutional address: Laboratory of Clinical Science National Institute of Mental Health Bethesda MD 20892. (REFERENCE 19 OF 55) 90170898 Hollander E DeCaria CM Schneier FR Schneier HA Liebowitz MR Klein DF Fenfluramine augmentation of serotonin reuptake blockade antiobsessional treatment. J Clin Psychiatry 1990 Mar;51(3):119-23 Seven patients who met DSM-III-R criteria for obsessive compulsive disorder and had only a partial response to the serotonin reuptake blockers fluoxetine, fluvoxamine, or clomipramine or were unable to tolerate therapeutic doses of these agents due to side effects underwent open treatment with fenfluramine augmentation. Fenfluramine is a serotonin releaser and reuptake blocker which is marketed as an anorectic agent. In doses of 20 to 60 mg/day, fenfluramine augmentation was well tolerated and resulted in a further decrease in obsessions and compulsions in six of these patients. Larger controlled studies are needed to confirm this finding. Institutional address: Department of Psychiatry College of Physicians and Surgeons Columbia University New York NY 10032. (REFERENCE 20 OF 55) 90130353 Jenike MA Approaches to the patient with treatment-refractory obsessive compulsive disorder. J Clin Psychiatry 1990 Feb;51 Suppl:15-21 Modern therapies have dramatically improved the treatment outcome for patients with obsessive compulsive disorder (OCD), but many clinicians are not aware of what is presently available in terms of effective treatments. Clinicians now know that if patients receive appropriate treatment, usually consisting of behavior therapy and/or psychotropic medication, the majority will improve substantially, and occasionally completely, within a few months. This article reviews some of the treatment options for managing refractory patients with OCD. Institutional address: Department of Psychiatry and Research Training Harvard Medical School Boston MA. (REFERENCE 21 OF 55) 90110004 Gorman JM Papp LA Chronic anxiety: deciding the length of treatment. J Clin Psychiatry 1990 Jan;51 Suppl:11-5 Anxiety disorders are chronic illnesses requiring long-term treatment. Relapse is typical and should not be considered treatment failure. Although the general guiding principle of pharmacotherapy for anxiety disorders--the lowest effective dose for the shortest possible time--remains, this rule should not interfere with the judicious use of medications as long as the benefits justify it. Although most antianxiety drugs are safe and have no long-term side effects, periodic drug discontinuation should be attempted. Establishing a secure and specific diagnosis and ruling out concomitant psychiatric and medical illnesses will augment the success of pharmacotherapy. The efficacy of nonpharmacologic treatments alone is, with very few exceptions, unsubstantiated at present; however, nonpharmacologic techniques may well supplement medication trials. Based on these principles and on the available data, specific recommendations are given for treating patients with generalized anxiety disorder, panic disorder, social phobia, and obsessive compulsive disorder. Institutional address: Department of Clinical Psychobiology New York State Psychiatric Institute New York. (REFERENCE 22 OF 55) 89291777 Bodkin JA White K Clonazepam in the treatment of obsessive compulsive disorder associated with panic disorder in one patient [see comments] J Clin Psychiatry 1989 Jul;50(7):265-6 The authors present the case of a 21-year-old man with obsessive compulsive disorder (OCD) complicated by panic disorder, whose OCD and panic symptoms resolved during clonazepam treatment. Prior treatment with an equivalent dose of lorazepam had ameliorated his panic attacks without affecting his obsessions or compulsions. Clonazepam worked with a rapidity and completeness uncharacteristic of more established treatments for OCD. Institutional address: McLean Hospital Belmont MA 02178. *****JOURNAL OF NERVOUS AND MENTAL DISEASE***** (REFERENCE 23 OF 55) 85236287 Baxter LR Jr Two cases of obsessive-compulsive disorder with depression responsive to trazodone. J Nerv Ment Dis 1985 Jul;173(7):432-3 Two patients with severe obsessive-compulsive disorder with superimposed depression, who had failed to respond to a wide variety of antidepressants, were treated with trazodone hydrochloride. Both seemed to obtain a rapid and impressive improvement in both their depression and obsessive-compulsive disorder while receiving trazodone. One patient subsequently had a monoamine oxidase inhibitor added to his treatment and experienced some additional improvement, but most of his improvement had occurred earlier, while he was receiving trazodone only. *** *** *****ACTA PSYCHIATRICA SCANDINAVICA***** (REFERENCE 24 OF 55) 87181026 Mahgoub OM A remarkable response of chronic severe obsessive-compulsive neurosis to phenelzine. Acta Psychiatr Scand 1987 Feb;75(2):222-3 The author describes a 22-year-old male who suffered from chronic severe Obsessive-Compulsive Neurosis (OCN) complicated by frequent depressive episodes. Administering the monoamine oxidase inhibitor phenelzine in high dosage led to complete alleviation of his depression in 10 weeks, and 3 weeks afterwards the OCN was markedly improved. The illness relapsed shortly after discontinuance of the drug. *****ACTA PSYCHIATRICA SCANDINAVICA. SUPPLEMENTUM***** (REFERENCE 25 OF 55) 88045902 Modigh K Antidepressant drugs in anxiety disorders. Acta Psychiatr Scand Suppl 1987;335:57-74 The efficacy of tricyclic antidepressants and monoamine oxidase inhibitors (MAOI) in the treatment of panic syndromes (panic disorder and agoraphobia with panic attacks) and obsessive-compulsive disorders is reviewed. Imipramine has been reported as significantly more effective against panic attacks than placebo or other psychoactive drugs in 12 of 16 studies. Clomipramine has been found superior to placebo or other psychoactive drugs in 5 controlled studies. The effectiveness of these drugs is also reflected in a large number of open trials. The MAOI phenelzine has been reported to be effective in 5 controlled studies. Clomipramine is the best documented drug in the treatment of obsessive-compulsive disorders. Its effectiveness has been documented in 7 controlled studies. Most investigators consider the effects in panic syndromes as well as in obsessive-compulsive disorders to be unrelated to the antidepressant effect. Institutional address: Department II S:t Jorgen Hospital Goteborg Sweden. *****AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY***** (REFERENCE 26 OF 55) 88293400 Morstyn R Clomipramine in obsessional disorders: a cautionary tale. Aust N Z J Psychiatry 1988 Jun;22(2):190-4 The author examines some dilemmas raised by the increasing use of clomipramine in the treatment of obsessional disorders. He presents a case vignette to illustrate some diagnostic, therapeutic and ethical concerns and suggests that by asking certain questions, pitfalls can be avoided. *****BIOLOGICAL PSYCHIATRY***** (REFERENCE 27 OF 55) 87242659 Zohar J Insel TR Obsessive-compulsive disorder: psychobiological approaches to diagnosis, treatment, and pathophysiology. Biol Psychiatry 1987 Jun;22(6):667-87 The diagnosis, treatment, and pathophysiology of obsessive-compulsive disorder (OCD) were examined in a series of studies utilizing psychobiological approaches. Putative biological markers previously reported in depression were studied in this disorder and revealed that on some measures [Dexamethasone Suppression Test and rapid eye movement (REM) latency on sleep electroencephalogram (EEG)], OCD patients resemble those with major depressive disorder (MDD), whereas on others [REM density, platelet serotonin uptake, probably platelet 3H-imipramine binding, and 5-hydroxy-indoleacetic acid (5-HIAA) in cerebral spinal fluid (CSF)] they do not. The relationship between OCD and MDD was further explored in a double-blind, randomized crossover study designed to compare the antiobsessional effects of two tricyclic antidepressants, clomipramine (CMI) and desipramine (DMI), in a nondepressed cohort of OCD patients. CMI was found to have significant antiobsessional effects in this group, whereas in the same patients, DMI lacked therapeutic effects. These results suggest that not all antidepressants are antiobsessive and that some property of CMI, such as its potent serotonergic effects, may be of pathophysiological relevance for OCD. The role of serotonin in this disorder was then tested using the pharmacological challenge strategy. A novel serotonin postsynaptic receptor (5HT-1) agonist, m- chlorophenylpiperazine (m-CPP), was administered orally (0.5 mg/kg) under double-blind, placebo-controlled conditions to OCD patients and controls. In addition, a serotonergic receptor antagonist, metergoline (4 mg), was given to a subset of OCD patients. Relative to healthy volunteers, the OCD patients became significantly more anxious, depressed, and dysphoric after m-CPP administration. Moreover, in the OCD patients, obsessive-compulsive symptoms increased markedly after m-CPP and decreased significantly following metergoline administration. These results demonstrate that agents that bind to the 5HT-1 receptor can acutely affect the symptoms of OCD patients. The striking behavioral effects of these direct postsynaptic receptor ligands and the relative specificity of clomipramine as an antiobsessional agent suggest that serotonergic neurons may play a role in the pathophysiology, as well as mediating the pharmacological reduction, of obsessional symptoms. (REFERENCE 28 OF 55) 86026553 Insel TR Mueller EA Alterman I Linnoila M Murphy DL Obsessive-compulsive disorder and serotonin: is there a connection? Biol Psychiatry 1985 Nov;20(11):1174-88 Reports of the antiobsessional efficacy of clomipramine have led to a "serotonin hypothesis" of obsessive-compulsive disorder (OCD). To test this hypothesis, 16 outpatients with DSM-III OCD were studied using several measures of serotonergic function. Platelet 3H- imipramine binding and serotonin uptake were not significantly different between the OCD patients and a normal, age-matched control group. The level of the metabolite 5-hydroxyindoleacetic acid (5- HIAA) in cerebrospinal fluid (CSF) was significantly higher in a small cohort of obsessionals compared with healthy volunteers, possibly reflecting increased brain serotonin turnover. In a direct test of the role of serotonin uptake in clomipramine's antiobsessional effects, the serotonin uptake inhibitor zimelidine was compared with the noradrenergic uptake inhibitor desipramine in a double-blind, controlled study. Zimelidine reduced CSF 5-HIAA, but was clinically ineffective in this group. Desipramine had weak but significant clinical effects. Nonresponders to zimelidine or desipramine improved significantly during a subsequent double blind trial of clomipramine. These findings demonstrate that pharmacological blockade of serotonin reuptake alone is not sufficient for an antiobsessional response. *****BRITISH JOURNAL OF PSYCHIATRY***** (REFERENCE 29 OF 55) 91121277 Delgado PL Goodman WK Price LH Heninger GR Charney DS Fluvoxamine/pimozide treatment of concurrent Tourette's and obsessive- compulsive disorder. Br J Psychiatry 1990 Nov;157:762-5 A 25-year-old man with a history of Tourette's syndrome presented for treatment of OCD symptoms. Fluvoxamine worsened tics, led to coprolalia, and did not help the OCD. The addition of pimozide dramatically reduced both OCD and Tourette's symptoms. Double-blind sequential discontinuation of fluvoxamine and pimozide confirmed that pimozide alone reduced only tics and the combination of fluvoxamine and pimozide was required for the improvement in OCD. Tics may reflect a subtype of OCD. Some OCD patients unresponsive to a 5-HT reuptake inhibitor alone may benefit from the addition of a dopamine antagonist. Institutional address: Department of Psychiatry Yale University School of Medicine West Haven Connecticut 06516. (REFERENCE 30 OF 55) 90123763 Tyrer P Murphy S Efficacy of combined antidepressant therapy in resistant neurotic disorder [see comments] Br J Psychiatry 1990 Jan;156:115-8 A 35-year-old woman with persistent affective and phobic symptoms responded dramatically to a combination of isocarboxazid and amitriptyline, and this improvement was maintained over the next three-and-a-half years. Isocarboxazid was replaced by placebo, using double-blind procedure. The change to placebo was accompanied by a marked increase in anxiety and depressive symptoms, which resolved when active isocarboxazid was reintroduced. It is suggested that combined antidepressant therapy still has a place in the treatment of resistant neurotic disorder. Institutional address: St Charles' Hospital London. *****BRITISH JOURNAL OF PSYCHIATRY. SUPPLEMENT***** (REFERENCE 31 OF 55) 90122159 Murphy DL Zohar J Benkelfat C Pato MT Pigott TA Insel TR Obsessive-compulsive disorder as a 5-HT subsystem-related behavioural disorder. Br J Psychiatry Suppl 1989 Dec(8):15-24 Involvement of the brain serotonin (5-HT) neurotransmitter system in obsessive-compulsive disorder (OCD) was originally suggested on the basis of therapeutic effects found with the semiselective serotonin uptake inhibitor, clomipramine. More recent studies directly comparing clomipramine with non-selective or norepinephrine-selective uptake inhibitors, such as desipramine or nortriptyline, as well as studies with new, more selective serotonin uptake inhibitors, including fluvoxamine and fluoxetine, have supported that hypothesis. Clomipramine's antiobsessional effect has been augmented with the serotonin precursor, L-tryptophan, or with lithium, which has prominent serotonergic effects. Patients whose OCD symptoms improved on clomipramine worsened when the drug was discontinued (regardless of duration of therapy) and improved when clomipramine was reinstituted. OCD symptoms also worsened when metergoline, a 5-HT antagonist, was given to patients who had improved with clomipramine. Metergoline given alone had no effect. Administration of m- chlorophenylpiperazine (m-CPP), a 5-HT receptor agonist, to untreated OCD patients increased their anxiety, depression, and dysphoria, and exacerbated their OC symptoms. After 4 months of clomipramine therapy, m-CPP failed to produce the same behavioural effects, suggesting an alteration of a 5-HT subsystem (possibly downregulation of some 5-HT receptors). The data reviewed suggest an important role for an abnormal brain 5-HT subsystem in patients with OCD. Institutional address: Laboratory of Clinical Science National Institute of Mental Health Bethesda Maryland. *****CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DE PSYCHIATRIE***** (REFERENCE 32 OF 55) 88079840 Primeau F Fontaine R Obsessive disorder with self-mutilation: a subgroup responsive to pharmacotherapy. Can J Psychiatry 1987 Nov;32(8):699-701 Obsessive-compulsive disorder (OCD) can be considered a complex entity with possibly different subgroups responsive to specific treatment. This article presents two cases of OCD with self- mutilation, successfully treated with serotonergic antidepressants. The authors discuss a sub-group of OCD patients whose rituals present as self-destructive behavior and are responsive to pharmacotherapy. Institutional address: Clinical Psychopharmacology Unit Allan Memorial Institute Royal Victoria Hospital Montreal Quebec. *****CLINICAL NEUROPHARMACOLOGY***** (REFERENCE 33 OF 55) 91004097 Hermesh H Aizenberg D Munitz H Trazodone treatment in clomipramine-resistant obsessive-compulsive disorder. Clin Neuropharmacol 1990 Aug;13(4):322-8 Trazodone (TZ) was administered to nine patients suffering from obsessive-compulsive disorder (OCD), who failed to respond to either clomipramine (CMI) or to CMI plus lithium carbonate. The group, as a whole, showed significant but mild improvement. Three patients responded very favorably to TZ. In these three responders, efficacy was substantiated by the return of the original obsessive-compulsive (OC) symptoms following TZ withdrawal and their amelioration after its readministration. Interestingly, the aggravation of OCD symptomatology that has been associated with a specific TZ metabolite was not observed. This study is consistent with previous reports of the anti-OC efficacy of TZ and suggests the involvement of complex serotonergic mechanisms in the pathophysiology of this disorder. Institutional address: Gehah Psychiatric Hospital Beilinson Medical Center Petah Tikva Israel. *****COMPREHENSIVE PSYCHIATRY***** (REFERENCE 34 OF 55) 91092092 Mavissakalian M Hamann MS Jones B Correlates of DSM-III personality disorder in obsessive-compulsive disorder. Compr Psychiatry 1990 Nov-Dec;31(6):481-9 Forty-three patients with primary obsessive-compulsive disorder (OCD) completed the Personality Diagnostic Questionnaire (PDQ), a self- rating scale designed to assess axis II personality disorders (PD) from DSM-III. Results showed that 53% of the patients received at least one PD diagnosis. The most frequent diagnoses were avoidant (30%), histrionic (26%), dependent (19%), and schizotypal (16%). Consideration of the personality traits irrespective of diagnostic category showed that in addition to avoidant and dependent personality characteristics, the sample had strong passive aggressive and compulsive tendencies and substantial histrionic, paranoid, and schizotypal traits. Patients exhibiting a greater number of personality traits were also significantly more symptomatic. However, anxiety, phobic, and obsessive-compulsive symptoms were not selected as unique predictors of any personality variables in the regression analyses. Rather, the most important correlate of PD in these patients consisted of dysphoric mood as assessed by the Beck Depression Inventory (BDI) and, to a lesser degree, younger age or shorter duration of illness. These findings do not support a specific link between OCD and PD in general and compulsive PD in particular. Institutional address: Department of Psychiatry Ohio State University College of Medicine Columbus 43210. *****DRUGS***** (REFERENCE 35 OF 55) 90183818 McTavish D Benfield P Clomipramine. An overview of its pharmacological properties and a review of its therapeutic use in obsessive compulsive disorder and panic disorder. Drugs 1990 Jan;39(1):136-53 During the 20 years that have elapsed since clomipramine (chlorimipramine) was first marketed, it has become well established in the treatment of depressive illness, particularly treatment- resistant depression. However, in addition to its role as an antidepressant, attention is being focused on the use of clomipramine in 2 other areas of psychiatry: obsessive compulsive disorder and panic disorder. Short term clinical trials have shown that clomipramine is generally more effective than amitriptyline, imipramine, desipramine, nortriptyline or clorgiline in reducing obsessive compulsive symptoms. Clomipramine appears to produce some short term benefit with exposure therapy in patients with obsessive compulsive disorder. However, the efficacy of the drug after long term follow-up has not been fully investigated. The antiobsessional efficacy of clomipramine appears to be independent of its antidepressant activity. In patients with panic disorder with or without agoraphobia (DSM-IIIR), clomipramine reduces the frequency and severity of panic attacks within 7 to 21 days of beginning treatment and efficacy is maintained for at least 12 months. Clomipramine is more effective than imipramine, the generally accepted standard treatment for patients with panic disorder after 2 weeks' treatment, but after 6 or 10 weeks both drugs are similarly effective. Other double-blind studies have shown that clomipramine is more effective than placebo and at least as effective as fluvoxamine and oxitriptan (5-hydroxytryptophan) in reducing panic attacks and associated anxiety. Adverse effects associated with clomipramine treatment are mild to moderate in nature and are predominantly a result of the drug's anticholinergic activity. The incidence of seizures is dose related, occurring in 0.48% of all patients receiving clomipramine less than or equal to 250 mg/day and 2.1% of patients receiving greater than or equal to 300 mg/day. In conclusion, the available data indicate that clomipramine is a worthwhile addition to the limited treatments available for obsessive compulsive disorder and panic disorder, two psychiatric disorders which have previously been difficult to manage pharmacologically. Institutional address: ADIS Drug Information Services Auckland New Zealand. *****ENCEPHALE***** (REFERENCE 36 OF 55) 91005927 Klein DF Pharmacotherapy of obsessive-compulsive disorder. Encephale 1990 Jul-Aug;16 Spec No:331-4 Due to its chronic and refractory nature, a wide variety of medications have been used in the treatment of obsessive-compulsive disorder (OCD). The most promising development has been with the tricyclic antidepressant clomipramine (Anafranil). More recently, a series of well controlled double blind studies have documented that clomipramine is more effective than placebo in reducing OCD symptoms. In a review of all 7 CMI studies with a total of 106 patients, two- thirds were found to be significantly improved on blind ratings (Insel and Zohar, 1988). Controlled studies also suggest clomipramine is more effective than other antidepressants for the treatment of OCD. Oral m-CPP (m-chlorophenyl piperazine), a selective 5HT agonist, has been found to increase obsessions in OCD patients when given acutely (Zohar, 1987; Hollander, 1988). This effect has been shown to decrease after chronic treatment with clomipramine (Zohar et al., 1988) or fluoxetine (Hollander et al., unpublished observations), suggesting that chronic treatment may correct serotonin dysregulation. Institutional address: College of Physicians & Surgeons Columbia University Department of Psychiatry New York 10032. *****INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY***** (REFERENCE 37 OF 55) 88034288 Kahn RS Westenberg HG Verhoeven WM Gispen-de Wied CC Kamerbeek WD Effect of a serotonin precursor and uptake inhibitor in anxiety disorders; a double-blind comparison of 5-hydroxytryptophan, clomipramine and placebo. Int Clin Psychopharmacol 1987 Jan;2(1):33-45 A double-blind placebo-controlled study of 5-HTP and clomipramine was carried out on 45 patients suffering from anxiety disorders (DSM- III). Clomipramine has shown to be effective in that it induced significant improvement on all rating scales as compared to placebo. 5-HTP showed a moderate reduction of the symptomatology on the 90- item symptoms checklist (SCL-90) and the State Scale of the Spielberger State-Trait Anxiety Inventory. Clomipramine and 5-HTP differed in their efficacy in that 5-HTP did not affect the associated depressive symptomatology. The results support the hypothesis that brain serotonergic pathways are involved in the pathogenesis of anxiety disorders, particularly in agoraphobia and panic disorders. Institutional address: Department of Biological Psychiatry University Hospital Utrecht The Netherlands. (REFERENCE 38 OF 55) 87196215 Mattes JA A pilot study of combined trazodone and tryptophan in obsessive- compulsive disorder. Int Clin Psychopharmacol 1986 Apr;1(2):170-3 An open pilot trial of combined trazodone and tryptophan for 11 patients with Obsessive-Compulsive Disorder was conducted to test the hypothesis that increasing serotonin activity is therapeutic for this condition. Results were not encouraging; several patients tolerated the combination poorly, but even among patients completing 2 weeks' treatment benefit was marginal. *****JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY***** (REFERENCE 39 OF 55) 91294376 McDougle CJ Price LH Goodman WK Charney DS Heninger GR A controlled trial of lithium augmentation in fluvoxamine-refractory obsessive-compulsive disorder: lack of efficacy. J Clin Psychopharmacol 1991 Jun;11(3):175-84 Two- and 4-week double-blind placebo-controlled trials of lithium augmentation of ongoing fluvoxamine treatment trials were conducted in 20 and 10 patients, respectively, with primary obsessive- compulsive disorder (OCD) who had failed to respond to fluvoxamine alone. Although 2 weeks of double-blind lithium augmentation produced a small but statistically significant reduction in obsessive- compulsive symptoms, most patients did not have a clinically meaningful response. Furthermore, there was no statistical or clinical improvement in obsessive-compulsive symptoms during the subsequent 4-week double-blind, placebo-controlled trial of lithium augmentation. On the basis of treatment response criteria, only 18% and 0% of the patients responded to lithium augmentation of fluvoxamine during the 2- and 4-week treatment trials, respectively. In light of the previously reported 44% response rate to lithium augmentation in treatment-resistant depressed patients on fluvoxamine, the results of this study suggest that pathophysiological differences may exist between OCD and depression. The routine use of lithium augmentation in the management of patients with OCD who are refractory to serotonin reuptake inhibitors is not supported by these findings. Institutional address: Department of Psychiatry Yale University School of Medicine New Haven Connecticut. (REFERENCE 40 OF 55) 90330774 Murphy DL Pato MT Pigott TA Obsessive-compulsive disorder: treatment with serotonin-selective uptake inhibitors, azapirones, and other agents. J Clin Psychopharmacol 1990 Jun;10(3 Suppl):91S-100S Obsessive-compulsive disorder (OCD) has recently been recognized as a relatively common disorder, affecting one in 40 individuals in the United States. OCD has also been demonstrated to be at least partially drug-responsive, although fewer than 20 adequate, fully controlled treatment trials in OCD patients have been reported, all in the last decade. The partially selective serotonin (5- hydroxytryptamine, 5-HT) uptake inhibitor clomipramine has been the most studied drug and uniformly has been found to be of some benefit in patients with OCD. Several recent controlled trials with other, more highly selective 5-HT uptake inhibitors have also shown these drugs to be more effective than placebo. More recently, preliminary data from several studies have questioned whether buspirone, an azapirone with prominent 5-HT-related anxiolytic and possible antidepressant properties, may have direct therapeutic effects in OCD patients or may be a useful adjunct when used in combination with the selective 5-HT uptake inhibitor fluoxetine. These studies are reviewed briefly and evaluated in the context of investigations that used other drugs with serotonergic actions either alone or in combination with selective 5-HT uptake inhibitors in OCD patients. Institutional address: Laboratory of Clinical Science NIMH NIH Clinical Center Bethesda MD 20892. (REFERENCE 41 OF 55) 90257104 Jenike MA Baer L Greist JH Clomipramine versus fluoxetine in obsessive-compulsive disorder: a retrospective comparison of side effects and efficacy. J Clin Psychopharmacol 1990 Apr;10(2):122-4 Since it will be some time until data will be available comparing clomipramine and fluoxetine for the treatment of patients with obsessive-compulsive disorder (OCD), a meta-analysis of previous studies was performed in an attempt to gain some information about comparable efficacy and side effects of these two commonly used agents. In 31 OCD patients receiving clomipramine in a controlled trial and 72 OCD patients receiving fluoxetine openly, both drugs appeared effective, with clomipramine having a somewhat larger effect than fluoxetine. Different side effect profiles may have a bearing on patient selection. Institutional address: Harvard Medical School Belmont Massachusetts Boston. (REFERENCE 42 OF 55) 88116140 Joffe RT Swinson RP Methylphenidate in primary obsessive-compulsive disorder. J Clin Psychopharmacol 1987 Dec;7(6):420-2 An acute methylphenidate challenge was performed on 13 patients with primary obsessive-compulsive disorder. There was no overall effect of methylphenidate on mood or obsessive-compulsive behavior. However, on various behavioral scales, four patients had an antiobsessive- compulsive response and one patient an antidepressant response to methylphenidate. The clinical and theoretical implications of these findings are discussed. Institutional address: Department of Psychiatry St. Michael's Hospital Toronto Ontario Canada. (REFERENCE 43 OF 55) 87138437 Jenike MA Armentano ME Baer L Disabling obsessive thoughts responsive to antidepressants. J Clin Psychopharmacol 1987 Feb;7(1):33-5 The authors report four patients with disabling obsessive thoughts who responded in dramatic fashion to antidepressant medication. None met criteria for major depression. This response is discussed in light of the current literature on obsessive-compulsive disorder. (REFERENCE 44 OF 55) 85131899 Tollefson G Alprazolam in the treatment of obsessive symptoms. J Clin Psychopharmacol 1985 Feb;5(1):39-42 Four patients with obsessive-compulsive disorder (DSM-III and RDC) were treated in an open trial with alprazolam. Moderate to marked improvement was noted in the degree of obsessionality, anxiety with motor tension, and secondary affective changes. The mixed anxiolytic- antidepressant properties of alprazolam are theorized as the basis for the clinical remissions. *****JOURNAL OF NEUROLOGY, NEUROSURGERY AND PSYCHIATRY***** (REFERENCE 45 OF 55) 90339051 Moore AP Macfarlane IA Blumhardt LD Neuroleptic malignant syndrome and hypothyroidism. J Neurol Neurosurg Psychiatry 1990 Jun;53(6):517-8 Two patients with primary hypothyroidism who developed neuroleptic malignant syndrome (NMS) are described. Thyroid disease might predispose to NMS by altering brain dopamine metabolism. Institutional address: Department of Neurological Science University of Liverpool Walton Hospital Liverpool United Kingdom. *****MINNESOTA MEDICINE***** (REFERENCE 46 OF 55) 89218802 Kim SW Dysken MW New findings in obsessive-compulsive disorder. Minn Med 1989 Feb;72(2):91-3, 110 During the past several years, impressive progress has been achieved in the field of obsessive-compulsive disorder (OCD). Improved diagnosis and treatment of this disorder has brought about renewed interest and optimism. Newer biological findings as well as drug treatment of obsessive-compulsive disorder are summarized here. A brief clinical description of obsessive-compulsive disorder is also included. *****NEUROPSYCHOBIOLOGY***** (REFERENCE 47 OF 55) 86257754 Prasad A Efficacy of trazodone as an anti-obsessional agent. Neuropsychobiology 1986;15 Suppl 1:19-21 Eight patients with chronic obsessive-compulsive neurosis were subjected to trazodone, an antidepressant acting on the serotonergic system. After 4 weeks of treatment, 6 showed significant reduction in the obsessional symptoms which was sustained after a 6-week follow- up. The 2 patients who did not show improvement had a significantly higher trait score than the others on psychometric ratings. *****PHARMACOLOGY, BIOCHEMISTRY AND BEHAVIOR***** (REFERENCE 48 OF 55) 85166614 Prasad A Efficacy of trazodone as an anti obsessional agent. Pharmacol Biochem Behav 1985 Feb;22(2):347-8 Eight patients with chronic Obsessive-Compulsive Neurosis were subjected to Trazodone, an antidepressant acting on the serotinergic system. After 4 weeks of treatment, 6 showed significant reduction in the obsessional symptoms which was sustained after a 6-week follow- up. The 2 patients who did not show improvement had a significantly higher trait score than the others on psychometric ratings. *****PHARMACOTHERAPY***** (REFERENCE 49 OF 55) 90318893 Jermain DM Crismon ML Pharmacotherapy of obsessive-compulsive disorder. Pharmacotherapy 1990;10(3):175-98 Obsessive-compulsive disorder (OCD) is a potentially devastating illness, both to the patient and family members. Its etiology is unclear, but some evidence points toward dysfunction in an orbitofrontal striatal-limbic neuronal loop. Although many agents have been used, clomipramine, a tricyclic antidepressant, appears to be the most promising therapy. Clomipramine was approved by the Food and Drug Administration and released for general use in early 1990 under the brand name Anafranil. Clomipramine's adverse effect profile is similar to that of currently marketed tricyclic antidepressants; however, it is associated with a higher frequency of seizures, estimated to be 0.7%. Although other serotonergic agents such as fluoxetine have shown promise in OCD, they have been studied only in a limited number of patients. Other agents, with the possible exception of monoamine oxidase inhibitors, either have resulted in inconsistent improvement or have been reported in an anecdotal fashion. Institutional address: College of Pharmacy University of Texas Austin 78712. *****PSYCHIATRIC DEVELOPMENTS***** (REFERENCE 50 OF 55) 87260786 Towbin KE Leckman JF Cohen DJ Drug treatment of obsessive-compulsive disorder: a review of findings in the light of diagnostic and metric limitations. Psychiatr Dev 1987 Spring;5(1):25-50 Nearly every category of psychotropic drug has been investigated in an attempt to find a pharmacologic treatment for obsessive compulsive disorder (OCD). This study reviews published trials from the English literature in which tricyclic antidepressants, monoamine oxidase inhibitors, neuroleptics, benzodiazepines, and other agents were employed for treatment of OCD. Weaknesses in the current methodology including diagnosis, measurement of severity and criteria for improvement have contributed to invalid conclusions about drug treatment and efficacy. It appears that OCD is an etiologically heterogeneous disorder with a complex differential diagnosis. For the clinician, a major conclusion drawn from this review is that no agent emerges as a drug of choice. Although clorimipramine, the most actively investigated agent, shows some promise, it has not been conclusively demonstrated that other, more readily available heterocyclic agents are less effective. Furthermore, when other disorders co-exist, such as panic disorder, alternative agents may prove as effective. *****PSYCHOLOGICAL MEDICINE***** (REFERENCE 51 OF 55) 89042559 Lelliott PT Noshirvani HF Basoglu M Marks IM Monteiro WO Obsessive-compulsive beliefs and treatment outcome. Psychol Med 1988 Aug;18(3):697-702 Of 49 compulsive ritualizers one-third perceived their obsessive thoughts as a rational and felt that their rituals warded off some unwanted or feared event (the content of their obsessions). The more bizarre the obsessive belief the more strongly it was defended and 12% of cases made no attempt to resist the urge to ritualize. Neither fixity of belief nor resistance to compulsive urges were related to duration of illness. Patients with bizarre and fixed obsessive beliefs responded as well to treatment (all but three received exposure), as did patients whose obsessions were less bizarre and recognized as senseless. There was no difference in outcome between patients who initially found it hard to control their obsessions or never resisted the urge to ritualize and those who initially could control obsessions or resist rituals. One year after starting treatment, patients whose obsessions and compulsions had improved with treatment recognized their irrationality more readily and controlled their compulsive urges more easily. Beliefs appeared to normalize as a function of habituation. Institutional address: Department of Experimental Psychopathology Institute of Psychiatry London. *****PSYCHOPHARMACOLOGY BULLETIN***** (REFERENCE 52 OF 55) 91110828 Simeon JG Thatte S Wiggins D Treatment of adolescent obsessive-compulsive disorder with a clomipramine-fluoxetine combination. Psychopharmacol Bull 1990;26(3):285-90 Clomipramine has been reported to be effective in the treatment of obsessive-compulsive disorder (OCD). Children and adolescents, however, tolerate poorly the adverse effects of tricyclics. Fluoxetine and other serotonin re-uptake inhibitors also appear useful in OCD, and are safer than clomipramine. To maximize the therapeutic effects and minimize adverse effects, 6 adolescents with OCD were treated in single trials with a clomipramine-fluoxetine combination. Duration of combined drug therapy ranged from 4 weeks to more than 28 weeks. Patients were first treated with clomipramine alone; if improvement or adverse effects were unsatisfactory, they received the drug combination. Clinical global improvement with clomipramine alone was moderate in 3 patients and minimal in 3. With a combined clomipramine-fluoxetine therapy, improvements were marked in 5 patients, and moderate in 1. These improvements were obtained with relatively low daily doses: clomipramine at 25 to 50 mg, and fluoxetine at 20 to 40 mg. Adverse effects appeared greater and much less tolerable with clomipramine alone than with the clomipramine- fluoxetine combination. This drug combination was well tolerated. These preliminary data suggest that relatively low doses of a clomipramine-fluoxetine combination may potentiate therapeutic effects and minimize adverse effects in OCD patients. Larger controlled trials are suggested. Institutional address: Royal Ottawa Hospital Ontario Canada. (REFERENCE 53 OF 55) 90319306 DeVeaugh-Geiss J Katz R Landau P Goodman W Rasmussen S Clinical predictors of treatment response in obsessive compulsive disorder: exploratory analyses from multicenter trials of clomipramine. Psychopharmacol Bull 1990;26(1):54-9 Two multicenter, double-blind trials were conducted in adults with DSM-III (American Psychiatric Association 1980) defined Obsessive Compulsive Disorder (OCD), comparing clomipramine (Anafranil, CMI) up to 300 mg daily with placebo. Of 519 patients evaluated, 260 received CMI for up to 10 weeks. More than half of the CMI treated patients were significantly improved, approximately 30 percent were minimally improved, and 15 percent showed no improvement after CMI treatment. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to assess treatment effects and attempts were made to correlate change in Y- BOCS score from baseline with a number of baseline characteristics, including age, sex, duration of OCD, baseline Y-BOCS score, baseline Hamilton Rating Scale for Depression (HAM-D) score, presence or absence of secondary depression, and predominance of obsessions or compulsions. Pearson and/or Spearman correlations failed to reveal any statistically significant correlations between outcome and any of the baseline characteristics studied. While the differences were not statistically significant, it did appear that male patients and patients with a longer duration of illness may be less likely to respond to CMI treatment; however, the overall conclusion from this analysis is that none of the variables studied is a reliable predictor of responses to treatment with CMI. Institutional address: CIBA-GEIGY Corporation Pharmaceuticals Division Summit NJ 07901. (REFERENCE 54 OF 55) 90319292 Mavissakalian M Jones B Olson S Perel JM The relationship of plasma clomipramine and N-desmethylclomipramine to response in obsessive-compulsive disorder. Psychopharmacol Bull 1990;26(1):119-22 The clinical significance of the effects of pharmacotherapy and the relationship between plasma tricyclic concentrations and outcome in 33 obsessive-compulsive disorder (OCD) patients who completed 10 weeks of treatment with clomipramine (239.4 +/- 57.0 mg/day) were analyzed. Results revealed that at the end of treatment, OCD symptoms had decreased to a subclinical level in 15 (47%) patients and that nearly 33 percent of the sample was virtually symptom free. However, 1 out of 4 patients failed to improve. Analysis of plasma levels (clomipramine 169.9 +/- 102.1 ng/ml; N-desmethylclomipramine 379.0 +/- 160.6 ng/ml) revealed that responders had significantly higher clomipramine levels and a trend toward lower desmethylclomipramine/clomipramine ratios. A significant degree of correlation was also obtained between plasma levels of clomipramine, but not N-desmethylclomipramine, and post-treatment outcome measures. Institutional address: Department of Psychiatry The Ohio State University College of Medicine Columbus 43210. *****SCIENTIFIC AMERICAN***** (REFERENCE 55 OF 55) 89186820 Rapoport JL The biology of obsessions and compulsions [see comments] Sci Am 1989 Mar;260(3):82-9 Samuel Johnson kept darting through doorways; a teen-ager named Sergei is unable to stop washing. Such repetitive, ritualistic behavior can make a person unable to function. The author thinks obsessive-compulsive disorder has biological roots in specific brain structures; she has treated it with certain drugs initially developed as antidepressants. Institutional address: Child Psychiatry Branch National Institute of Mental Health.