Intravenous clomipramine for obsessive-compulsive disorder refractory to oral clomipramine: a placebo-controlled study.

BACKGROUND: Uncontrolled reports suggest that intravenous clomipramine hydrochloride may be effective for patients with obsessive-compulsive disorder (OCD) who are nonresponsive to oral clomipramine. METHODS: 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." RESULTS: 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. CONCLUSIONS: 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.

Lyme disease: a neuropsychiatric illness.

OBJECTIVE: Lyme disease is a multisystemic illness that can affect the central nervous system (CNS), causing neurologic and psychiatric symptoms. The goal of this article is to familiarize psychiatrists with this spirochetal illness. METHOD: Relevant books, articles, and abstracts from academic conferences were perused, and additional articles were located through computerized searches and reference sections from published articles. RESULTS: Up to 40% of patients with Lyme disease develop neurologic involvement of either the peripheral or central nervous system. Dissemination to the CNS can occur within the first few weeks after skin infection. Like syphilis, Lyme disease may have a latency period of months to years before symptoms of late infection emerge. Early signs include meningitis, encephalitis, cranial neuritis, and radiculoneuropathies. Later, encephalomyelitis and encephalopathy may occur. A broad range of psychiatric reactions have been associated with Lyme disease including paranoia, dementia, schizophrenia, bipolar disorder, panic attacks, major depression, anorexia nervosa, and obsessive-compulsive disorder. Depressive states among patients with late Lyme disease are fairly common, ranging across studies from 26% to 66%. The microbiology of Borrelia burgdorferi sheds light on why Lyme disease can be relapsing and remitting and why it can be refractory to normal immune surveillance and standard antibiotic regimens. CONCLUSIONS: Psychiatrists who work in endemic areas need to include Lyme disease in the differential diagnosis of any atypical psychiatric disorder. Further research is needed to identify better laboratory tests and to determine the appropriate manner (intravenous or oral) and length (weeks or months) of treatment among patients with neuropsychiatric involvement.

Childhood abuse, family environment, and outcome in bulimia nervosa.

BACKGROUND: About one third of patients with bulimia nervosa continue to do poorly despite intensive treatment. In an effort to identify historical factors that might differentiate patients who are persistently bulimic from patients who have fully recovered, we examined the relationship between long-term outcome and three factors: childhood trauma, family environment, and parental psychopathology. METHOD: Fifty-two women previously hospitalized for bulimia nervosa were interviewed 2 to 9 years later. In addition to structured diagnostic interviews, measures included the Family Environment Scale, the Family History interview, and a semistructured interview of childhood abuse. Outcome comparisons were made between the fully recovered and the women who still met DSM-III-R criteria for bulimia nervosa. RESULTS: Reports of childhood physical abuse and of a family environment characterized by low cohesion and high control were significantly associated with poor outcome. Characteristics of the family environment seemed to have greater influence on outcome than physical abuse alone. Sexual abuse in general was not associated with outcome. Outcome was not associated with comorbidity of Axis I or Axis II disorders or parental psychopathology. CONCLUSION: Aspects of the family environment of childhood may contribute to the course of bulimia nervosa. Definitive conclusions require a prospective study.

Hypochondriasis and obsessive compulsive disorder: overlaps in diagnosis and treatment.

BACKGROUND: Hypochondriasis is a disorder for which there are no established effective treatments. Hypochondriacs, in their obsessions about illness, compulsions to check with others, and failure to be reassured, share many features in common with those who have obsessive compulsive disorder (OCD). METHOD: The authors present a case series of six patients with DSM-III-R hypochondriasis, five of whom also had a history of OCD. Two of the six agreed to be treated with doses of fluoxetine typically used to treat OCD. RESULTS: Both patients, one of whom had no past history of OCD, showed a marked improvement in hypochondriacal symptoms. CONCLUSION: These findings suggest that a subgroup of patients with hypochondriasis may be particularly responsive to serotonin reuptake blockers.

Psychiatric manifestations of Lyme borreliosis.

BACKGROUND: Lyme borreliosis (Lyme disease), a tick-borne spirochetal illness, has later manifestations that may include arthritic, neurologic, ophthalmologic, and cardiac symptoms. Recent reports suggest psychiatric symptoms may also be part of the clinical picture. METHOD: Using a structured interview (SCID), we interviewed three patients who had developed a psychiatric disorder for the first time after infection with Borrelia burgdorferi. RESULTS: During Lyme borreliosis, one patient had major depression and panic disorder, one patient had an organic mood syndrome with both depression and mania, and the third patient had panic disorder. These disorders remitted after adequate antibiotic treatment. CONCLUSION: While depression has been previously linked to neuroborreliosis, this is the first report to link panic disorder and mania with borrelial infection. Because of the rapid rise of Lyme borreliosis nationwide and the need for antibiotic treatment to prevent severe neurologic damage, mental health professionals need to be aware of its possible psychiatric presentations.

Outcome and clinical course in inpatient bulimic women: a 2- to 9-year follow-up study.

BACKGROUND: One previous follow-up study suggested that inpatient bulimic women do quite poorly; after an interval of 2 to 5 years, only 13% were recovered. To examine the course and outcome of a sample of patients with bulimia nervosa that was severe enough to require inpatient hospitalization, the authors conducted the following study. METHOD: Women (N = 52) with DSM-III-R bulimia nervosa were sought 2 to 9 years after hospitalization. Prior to contact, a retrospective chart review was conducted to determine global functioning and admission diagnoses. At follow-up, patients participated in a 4 to 6 hour interview that assessed current and lifetime Axis I disorders (SCID-I), current Axis II disorders (PDE), eating behaviors (EAT, BSQ, EDI, PSR), global functioning (GAF), social adjustment (SAS-SR), and treatment and medical problems experienced since discharge. To assess the significance of differences between the recovered and the currently bulimic women, Yates-corrected chi-square tests and two-tailed t tests were used. RESULTS: Of the 52 women, 46 were interviewed, 1 had died, and 5 could not be located. Of the 46 interviewed women, 39% had fully recovered, 20% had partially recovered, and 41% were currently bulimic. The likelihood of recovery increased with length of time since discharge. While medical problems related to the bulimia were few, treatment with phenelzine was associated with three reports of serious hypertensive episodes, one of which led to death. Global functioning before hospitalization, lifetime DSM-III-R Axis I diagnoses, and current Axis II diagnoses were not associated with outcome. CONCLUSIONS: These findings suggest that even severely ill bulimic patients have a significant chance of achieving full recovery.

Medication therapy for social phobia.

Social phobia, though the third most common psychiatric disorder in the United States, has received little systematic attention until recently. Chronic and disabling symptoms usually precede other disorders in individuals with comorbidity, including alcohol abuse. Though about 80% of individuals do not seek treatment, controlled trials have demonstrated efficacy for several medications, of which phenelzine (an irreversible monoamine oxidase inhibitor [MAOI]) is the best studied. The benzodiazepines, clonazepam and alprazolam, also hold promise. New reversible MAOIs such as moclobemide and brofaromine are under investigation; fluoxetine and other serotonin selective reuptake inhibitors need further controlled study. The benefits of group cognitive-behavioral therapy also appear substantial. Issues for future investigation include long-term outcome, differential therapeutics, diagnostic subtyping, and combination treatments.

Functional impairment in social phobia.

BACKGROUND: This study examined the nature of impairment of functioning in persons with social phobia and assessed the validity of two new rating scales for describing impairment in social phobia. METHOD: In 32 patients with social phobia and 14 normal control subjects, impairment was assessed using the Disability Profile and the Liebowitz Self-Rated Disability Scale, new instruments designed to provide clinician- and patient-rated descriptive measures of current and lifetime functional impairment related to emotional problems. Validity of the new scales was assessed by measuring internal consistency, comparing scores for patients and controls, and comparing scores with those on standard measures of disability, social phobia symptoms, and social support. RESULTS: More than half of all social phobic patients reported at least moderate impairment at some time in their lives, due to social anxiety and avoidance, in areas of education, employment, family relationships, marriage/romantic relationships, friendships/social network, and other interests. Social phobic patients were rated more impaired than normal controls on nearly all items on both measures. Both scales were internally consistent, with Cronbach's alpha coefficients for lifetime and current disability subscales in the range of .87 to .92. Significant positive correlations of scores on the new scales with scores on coadministered standard scales of social phobia symptoms and disability demonstrated concurrent validity. Disability was not significantly correlated with measures of social support. CONCLUSION: Social phobia is associated with impairment in most areas of functioning, and the new scales appear useful in assessing functional impairment related to social phobia.

Treatment of social phobia with drugs other than benzodiazepines.

Social phobia is emerging as an important cause of psychiatric morbidity. Reasons for this are described, as are clinical issues of importance to social phobia, including the extensive associated distress and disability. The use of phenelzine, atenolol, buspirone, fluoxetine, and moclobemide are described. Diagnostic and transcultural aspects of social phobia are described.

The pharmacotherapy of moral or religious scrupulosity.

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.

Serotonergic medications for sexual obsessions, sexual addictions, and paraphilias.

BACKGROUND: Paraphilias and related disorders have recently been thought of as sexual addictions. However, it has also been argued that these disorders are sexual compulsions. The question arises as to whether these disorders and obsessive compulsive disorder respond in the same way to pharmacotherapy. METHOD: We retrospectively reviewed outcome in 13 patients who presented with sexual symptoms and were treated with serotonin reuptake blockers. Symptoms were divided into paraphilias, nonparaphilic sexual addictions, and sexual obsessions. RESULTS: Paraphilias had the least improvement, while sexual obsessions had the best response to medication. CONCLUSION: Paraphilias and related disorders may be less responsive than sexual obsessions or compulsions to serotonin reuptake blockers. Perhaps paraphilias and related disorders are on the impulsive rather than the compulsive end of the spectrum of obsessive compulsive disorders. Controlled trials are, however, necessary to replicate these preliminary findings.

Clomipramine treatment of panic disorder: pros and cons.

BACKGROUND: Controlled trials suggest that clomipramine may be a highly effective antipanic drug. Lowering the starting dose may alleviate troublesome initial side effects and increase acceptability and compliance. METHOD: Fifty-eight patients with DSM-III-R panic disorder with or without agoraphobia underwent 13 weeks of clomipramine treatment. Starting at 10 mg/day, the dose was gradually increased to a mean dose of 97 mg/day. RESULTS: While completers showed highly significant improvement, the benefits were severely limited by a high dropout rate due to adverse reactions occurring mostly during the first 2 weeks of treatment. CONCLUSION: Given the alternatives, clomipramine should not be used as a first-line antipanic medication.

The underdiagnosis of neuropsychiatric Lyme disease in children and adults.

Lyme Disease has been called "The New Great Imitator," a replacement for that old "great imitator" neurosyphilis. This article reviews the numerous psychiatric and neurologic presentations found in adults and children. It then reviews the features of Lyme Disease, which makes it almost uniquely hard to diagnose, including the complexity and unreliability of serologic tests. Clinical examples follow that illustrate those presentations of this disease that mimic attention deficit hyperactivity disorder (ADHD), depression, and multiple sclerosis.

Hypochondriasis and its relationship to obsessive-compulsive disorder.

Hypochondriasis is a heterogeneous disorder. This was well demonstrated in the study by Kellner et al, which showed that patients with high levels of disease fear tended to be more anxious or phobic, whereas patients with high levels of disease conviction tended to have more and more severe somatic symptoms. Little comorbidity exists to support the statement that hypochondriasis is an obsessive-compulsive spectrum disorder. Although patients exist whose hypochondriac concerns are identical in quality to the intrusive thoughts of patients with OCD, as a group, patients with hypochondriasis do not share a comorbidity profile comparable with that of patients with OCD. The data support a closer relationship between hypochondriasis and somatization disorder than between hypochondriasis and OCD. The family history data is limited by the lack of adequate studies. Using comparable methods of the family history approach, Black's study reported a higher frequency of GAD but not OCD among the relatives of OCD patients--a finding similar to what Noyes found among the relatives of hypochondriac patients; however, using the direct interview method, somatization disorder was the only statistically more common disorder, among relatives of female hypochondriac patients. Therefore, although the parallel in overlap with GAD is suggestive of a commonality between OCD, GAD, and hypochondriasis, the finding of a greater frequency of somatization disorder leans against the hypothesis that hypochondriasis is best considered an OCD spectrum disorder. The pharmacologic treatment data are the one type of biologic evidence that supports a bridge to OCD. The pharmacologic studies suggest that for patients with general hypochondriasis, TCAs are not effective and that higher dosages and longer trials of the SRIs are needed. These pharmacologic observations are comparable with the ones made for patients with OCD but dissimilar to the observations made for depression. The benefit of imipramine among patients with illness phobia must be assessed in placebo-controlled trials among illness phobics and among hypochondriacs. Even more valuable would be a direct comparison of a TCA (e.g., imipramine or desipramine) and a selective SRI (e.g., fluoxetine) to determine whether the response to selective SRIs is greater. Although the pharmacologic data are compelling in supporting the hypothesis that hypochondriasis is an obsessive-compulsive spectrum disorder, the comorbidity data are equally compelling in dispelling that hypothesis. Perhaps future studies clarify the subtypes of hypochondriasis, be they "phobic, obsessive, and depressive," "chronic and episodic," "early onset versus late onset" or some other as yet undetermined subtype. Such clarification may be aided by better instruments to assess the obsessive-compulsive and hypochondria spectrums within individuals and families and by neuropsychological or pharmacologic challenge and neuroimaging studies.

Obsessive-compulsive disorder: an overview.

In this article, which is the first in a three-part series, the authors provide an overview of the current state of our knowledge of the phenomenology, etiology, and diagnosis of OCD. The DSM-IV criteria for OCD are presented and explicated. Disorders that are commonly comorbid with OCD (e.g., major depressive disorder, other anxiety dis-orders, Tourette's disorder) are described. The authors also discuss disorders such as body dysmorphic disorder that may be related to OCD and are often termed OCD spectrum disorders. OCD is likely to have multiple causes and the authors discuss behavioral, neuroanatomical, and neurochemical theories of OCD. Two treatments have demonstrated efficacy in OCD, cognitive-behavioral therapy and pharmacotherapy with serotonergic reuptake inhibitors, and the authors discuss how these treatments may work in light of what is known about the etiology of the disorder. The different subtypes of OCD that have been proposed are described along with their implications for treatment. The article concludes with a discussion of diagnosis that provides specific guidance for the clinician on how to assess a patient for possible OCD. The next two articles in this series will cover cognitive-behavioral and medication treatment in detail.

Biological therapies for obsessive-compulsive disorder.

Two treatments have demonstrated efficacy in OCD, exposure and response (ritual) prevention (EX/RP) and pharmacotherapy with serotonin reuptake inhibitors (SRIs). In this article, which is the third in a three-part series, the authors present an overview of the role of biological treatments for OCD. The evidence for the efficacy of the serotonin reuptake inhibitors (clomipramine and the five selective serotonin reuptake inhibitors "SSRIs" fluvoxamine, fluoxetine, paroxetine, sertraline, and citalopram) as monotherapy for OCD is reviewed. The authors also discuss the rationale for choosing among these agents for specific patients. Research on other types of medication monotherapies for OCD is also discussed. The authors then cover strategies for treatment-resistant OCD, including combining EX/RP and SRI medication treatment, combining clomipramine and an SSRI, use of augmenting medications, and use of intravenous clomipramine. Findings concerning the use of other somatic therapies for treatment-resistant OCD, including electroconvulsive therapy, neurosurgery, plasma exchange/IV immunoglobulin/maintenance antibiotics, and transcranial magnetic stimulation, are also reviewed. Finally, the authors discuss what is known about matching treatments to patients with certain specific symptom clusters, how long to continue maintenance medication treatment, and how to terminate treatment.

Canadian Incidence Study of Reported Child Abuse and Neglect: methodology.

This article describes the methodology of the first Canada-wide study of the incidence and characteristics of reported child abuse and neglect. Child welfare investigators from a random sample of 51 child welfare service areas completed a three-page survey form describing the results of 7,672 child maltreatment reports received during the months of October to December 1998. The study documented a 90% participation rate and a 95% item completion rate. An estimated 135,571 child maltreatment investigations were completed, a rate of 21.52 investigated children per 1,000 children in Canada in 1998. The Canadian Incidence Study of Reported Child Abuse and Neglect is a rich database that will provide researchers with important contextual information on reported child maltreatment in Canada and a comprehensive source of information on factors associated with key service decisions made by child welfare investigators.

Asceticism: creative spiritual practice or pathological pursuit?

Asceticism in a religious context refers to a voluntary and sustained practice of self-denial in which immediate or sensual gratifications are renounced in order to attain a higher spiritual state (Kaelber 1987). Virtually all of the major world religions have within them a way in which the individual, through ascetic practices, can strive to achieve a more thorough absorption in the sacred. Although many psychiatrists might consider any ascetic or religious practice to be pathological, others take a more neutral view by emphasizing that religious or mystical practice can also be adaptive and creative (Group for the Advancement of Psychiatry 1976).

A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy.

BACKGROUND: Optimal treatment remains uncertain for patients with cognitive impairment that persists or returns after standard IV antibiotic therapy for Lyme disease. METHODS: Patients had well-documented Lyme disease, with at least 3 weeks of prior IV antibiotics, current positive IgG Western blot, and objective memory impairment. Healthy individuals served as controls for practice effects. Patients were randomly assigned to 10 weeks of double-masked treatment with IV ceftriaxone or IV placebo and then no antibiotic therapy. The primary outcome was neurocognitive performance at week 12-specifically, memory. Durability of benefit was evaluated at week 24. Group differences were estimated according to longitudinal mixed-effects models. RESULTS: After screening 3368 patients and 305 volunteers, 37 patients and 20 healthy individuals enrolled. Enrolled patients had mild to moderate cognitive impairment and marked levels of fatigue, pain, and impaired physical functioning. Across six cognitive domains, a significant treatment-by-time interaction favored the antibiotic-treated group at week 12. The improvement was generalized (not specific to domain) and moderate in magnitude, but it was not sustained to week 24. On secondary outcome, patients with more severe fatigue, pain, and impaired physical functioning who received antibiotics were improved at week 12, and this was sustained to week 24 for pain and physical functioning. Adverse events from either the study medication or the PICC line were noted among 6 of 23 (26.1%) patients given IV ceftriaxone and among 1 of 14 (7.1%) patients given IV placebo; these resolved without permanent injury. CONCLUSION: IV ceftriaxone therapy results in short-term cognitive improvement for patients with posttreatment Lyme encephalopathy, but relapse in cognition occurs after the antibiotic is discontinued. Treatment strategies that result in sustained cognitive improvement are needed.