Treatment-refractory Disorder Research Articles

Pathways controlling neurotoxicity and proteostasis in mitochondrial complex I deficiency.

Neuromuscular disorders caused by dysfunction of the mitochondrial respiratory chain are common, severe and untreatable. We recovered a number of mitochondrial genes, including electron transport chain components, in a large forward genetic screen for mutations causing age-related neurodegeneration in the context of proteostasis dysfunction. We created a model of complex I deficiency in the Drosophila retina to probe the role of protein degradation abnormalities in mitochondrial encephalomyopathies. Using our genetic model, we found that complex I deficiency regulates both the ubiquitin/proteasome and autophagy/lysosome arms of the proteostasis machinery. We further performed an in vivo kinome screen to uncover new and potentially druggable mechanisms contributing to complex I related neurodegeneration and proteostasis failure. Reduction of RIOK kinases and the innate immune signaling kinase pelle prevented neurodegeneration in complex I deficiency animals. Genetically targeting oxidative stress, but not RIOK1 or pelle knockdown, normalized proteostasis markers. Our findings outline distinct pathways controlling neurodegeneration and protein degradation in complex I deficiency and introduce an experimentally facile model in which to study these debilitating and currently treatment-refractory disorders.

A Naturalistic Study of Time to Recovery in Adults with Treatment-refractory Disorders

Objectives: Individuals with treatment-refractory disorders have high comorbidity. There is little information on whether recovery is possible and how long it might require. We focused on the individual’s recovery using a broad measure of psychopathology, regardless of the variety of disorders present. Methods: We recruited 226 adults [mean age 31.0, SD = 10.3; 75.2% female] entering residential treatment for treatment-refractory disorders to delineate their course and outcome. Individuals received periodic Longitudinal Interval Follow-along Evaluation interviews for symptoms and functioning variables for up to 14 years. Periodic psychodynamic and relationship vignette interviews were rated with the Psychodynamic Conflict Rating Scales (PCRS) for a subgroup of 54 subjects. Outcome variables included modeled rates of change, final scores, time to recovery, and time to attaining healthy adaptive functioning, using Kaplan-Meier estimates from time-to-event analyses. Results: Recovery of PCRS Pathological Functioning occurred in 12 (22%) of 54 subjects rated: median time-to-recovery = 11.63 years (CI: 9.64– upper number not calculable). Eight (14.81%) subjects also developed healthy adaptive functioning, with the time-to-attainment for the first quartile at 10.95 years (CI: 7.87 - upper bound not calculable). Recovery from psychopathology was significantly associated with a median percentage recovered in the domains of symptoms (64.29%), functioning (87.50%), and psychodynamic functioning (50%). Although attaining healthy adaptive functioning was less common, it was highly associated with already achieving recovery from dynamic psychopathology, [OR = 57.40, CI 5.80 – 567.83, p = .0001]. Conclusions: These results provided convergent validation of recovery in psychodynamic psychopathology. Some recovered individuals also attained healthy adaptive functioning, which took somewhat longer.

Platelet-rich plasma is a promising therapy for melasma.

Platelet-rich plasma (PRP) is an autologous blood product which has recently been used in multiple spheres of dermatology including facial rejuvenation, androgenetic alopecia, acne scars, and wound healing. Its use in melasma is comparatively an understudied topic. An extensive systematic literature search of the PubMed electronic database and Cochrane central register of controlled trials was done using the keywords "platelet rich plasma" and "melasma" in the title. Relevant studies were selected and data were analyzed by two different authors. Four articles were excluded as they did not adhere to the inclusion criteria of this review and a total of 6 articles were reviewed.The relevant references of the included articles were also traced and included. These studies showed that PRP has been used effectively not only as an adjuvant therapy but also as a standalone treatment for melasma. PRP contains about 30 growth factors, transforming growth factor beta (TGF-β) being one of the growth factors having a predominant role in treatment of melasma. TGF-β decreases signal transduction of microphthalmia-induced transcription factor and thus decreases tyrosinase and tyrosinase-related proteins. In addition to this, PRP also has an additional benefit of inducing collagen synthesis thus improving the quality and texture of the skin. But there is a scarcity of data and large randomized controlled trials. This review is an effort to highlight and upscale the use of this excellent blood product for melasma which is quite a treatment refractory disorder.

Readiness for First-In-Human Neuromodulatory Interventions.

Novel neurointerventions present innovative therapeutic approaches to a range of treatment-refractory disorders. We sought to characterize factors that inform and define translational readiness for first-in-human (FIH) neuromodulatory trials. We used a two-part methodology involving a scoping review of the biomedical literature on the readiness of FIH trials for both neurological and non-neurological applications, and semi-structured interviews with stakeholders about decision-making for neuromodulation using magnetic resonance-guided focused ultrasound as a case example. One hundred and thirty factors relevant to FIH readiness were identified in the scoping review. Trial design, adequacy of preclinical evidence, and risk were ubiquitous across biotechnologies. Target organ, target function, and inadequacy of animal models were dominant in the neurointervention literature. Interview results on the relative importance of these factors reveal divergent values, priorities, and understandings both between patients and clinicians and between patients affected by different conditions. Readiness of neurotechnology for FIH trials is defined by a multitude of interacting factors that pertain to clinical and nonclinical priorities, perceptions, and values.

612 – Audit of referrals to the tertiary affective disorders service in newcastle

NHS Specialist Services are commissioned by Regional Specialist Commissioners in accordance with the Specialised Services National Definitions Set (SSNDS). This sets out general and specific criteria defining the nature of patients who are viewed as appropriate for referral. The Regional Affective Disorder Service (RADS) in Newcastle is commissioned under such arrangements - SSNDS definition 22 (Mental Health), section 6 (complex and/or treatment refractory disorders). The aim of this audit is to assess the appropriateness of referrals to RADS based on SSNDS criteria. http://www.specialisedservices.nhs.uk/info/nhs-specialisedservices . This is a retrospective study: The referral and initial assessment letters of patients referred into RADS between January 2011and July 2011 were reviewed and scored against the criteria. We collected data on whether patients definitely, partially or didn’t meet the criteria. We also collected data on whether patients were referred from primary or secondary care and if they were a health care professional. 67 referrals were audited. 25% definitely met criteria (15 of them with bipolar disorder), 18% partially met criteria (11 unipolar) and 57% did not meet criteria. The reason for only partially meeting criteria was due commonly to meeting the pharmacological, but not psychotherapy criteria or not meeting the pharmacological criteria in details. Of those not meeting criteria, 8 were health care professionals being seen out of area, 2 from GPs for diagnosis clarification, 6 have a non-affective disorder diagnosis and 17 meet the general criteria but it was less clear that they met specific criteria. 5 did not meet either general or specific criteria.

First-Line Treatment for Pediatric Obsessive–Compulsive Disorder

Pediatric obsessive–compulsive disorder (OCD) is a common psychiatric disorder that impairs children’s functioning in home, school, and community settings. Once thought to be an untreatable or treatment refractory disorder, evidence-based treatments now exist for pediatric OCD. Various psychological treatment approaches for pediatric OCD have been investigated and research supports the use of cognitive-behavioral therapy (CBT) with exposure and response prevention (E/RP) and combined CBT/E/RP with serotonin reuptake inhibitor pharmacotherapy. This paper reviews these approaches and highlights the prominent role of CBT/E/RP as a first-line treatment for pediatric OCD.

Impulsive Phenomena, the Impulsive Character (der Triebhafte Charakter) and DSM Personality Disorders

Impulsive phenomena have frequently been associated with personality disorders, beginning with Reich's description of the impulsive-character (Reich, 1925/1975). However, questions remain regarding the cooccurrence of a wide variety of impulsive phenomena and whether an underlying structure influences the differential association of impulses to individual personality disorders. Adults entering residential treatment for treatment-refractory disorders were interviewed about their lifetime histories of 33 impulse items, following independent diagnostic interviews. Factor analysis suggested 12 underlying dimensions of impulsive phenomena, explaining 68% of the variance. Borderline and antisocial PDs had the highest impulse scores, followed by self-defeating, narcissistic, depressive, and passive-aggressive PDs. Schizoid, avoidant, obsessive-compulsive, and dependent types were negatively associated with impulsive phenomena. Individuals with the highest impulse scores showed higher levels of borderline, antisocial and either self-defeating or passive-aggressive personality pathology, and were characterized by high Neuroticism and Openness and low Agreeableness on the NEO-FFI. Personality disorders and the NEO-FFI personality traits both predicted unique variance in impulsive phenomena, with the former predominating. Our findings bear striking similarities to Reich's (1925/1975) descriptions of the impulsive character.

Pediatric Deep Brain Stimulation: A Cautionary Approach

Pediatric Deep Brain Stimulation: A Cautionary Approach

From the Guest Editor

Back to table of contents Next article FROM THE GUEST EDITORFull AccessFrom the Guest EditorCharles B. Nemeroff, M.D., Ph.D.Charles B. NemeroffSearch for more papers by this author, M.D., Ph.D.Published Online:1 Oct 2010https://doi.org/10.1176/foc.8.4.foc473AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail FOCUS is truly intended to provide continuing medication education for practitioners that will have an impact on their practice by presenting state-of-the-art, evidence-based medicine. This issue of FOCUS is of particular relevance to psychiatrists because it provides an update on treatment-refractory psychiatric disorders including major depression, anxiety disorders, and schizophrenia. Many patients with psychiatric disorders are treated by nonpsychiatrists including family physicians, general practitioners, and obstetricians/gynecologists. This situation is unavoidable because there are simply too few psychiatrists to treat the large numbers of patients who have these major psychiatric illnesses. Therefore, as psychiatrists, we are referred the substantial numbers of patients with mood and anxiety disorders that do not respond to monotherapy with commonly prescribed psychopharmacological agents such as selective serotonin reuptake inhibitors. In this issue of FOCUS, we provide overviews of the management of treatment-refractory depression, schizophrenia, and major anxiety disorders. In addition, we provide a look into the future by reviewing the emerging field of personalized medicine in psychiatry, which has the goal of reducing treatment failures in patients with these disorders by matching individual patients with the therapies most likely to successfully treat their symptoms, both psychopharmacologically and psychotherapeutically. As with all issues of FOCUS, we also have the unique opportunity to publish reprints of several of the seminal publications in the field in their entirety and abstracts of others. This will allow practitioners to have at their disposal in a single issue of the journal a summary of management of patients with treatment-refractory disorders. After reading the entire volume, one inexorable conclusion is reached—psychiatric treatment of these disorders remains far from optimal, and considerably more controlled clinical trials, as well as novel approaches, are needed to further advance the field. FiguresReferencesCited byDetailsCited byNone Volume 8Issue 4 Fall 2010Pages 473-473Psychopharmacology: Treatment-Resistant Disorders PDF download

Referral for Medical Evaluation: An Ethical Obligation?

Back to table of contents Next article Taking IssueFull AccessReferral for Medical Evaluation: An Ethical Obligation?Glenn D. Grace Ph.D., M.S.,Richard C. Christensen M.D., M.A.,Glenn D. Grace Ph.D., M.S.Search for more papers by this author,Richard C. Christensen M.D., M.A.Search for more papers by this author,Published Online:1 Jan 2010https://doi.org/10.1176/ps.2010.61.1.3AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Many behavioral health providers might believe that medical illnesses capable of producing psychological disorders are rare and unlikely to be a significant issue in mental health treatment. However, studies of both inpatient and outpatient clinical samples indicate that an alarming number of patients have unrecognized medical illnesses that directly cause or contribute to their psychiatric symptoms. If these illnesses are unrecognized and untreated, dire health consequences may result.From a best-practices perspective, it can be argued that a collaborative model of integrated primary and behavioral health care affords patients the greatest opportunity for optimal treatment and recovery. However, most systems that deliver behavioral health care are separated from primary care services by systemic and ideological chasms. Nevertheless, if a somatic illness is suspected to be an underlying cause of a psychiatric disorder, the mental health provider bears the responsibility of referring the patient for a more thorough medical evaluation.We contend that referring all psychiatric patients with newly diagnosed and treatment-refractory disorders for a medical evaluation is more than good practice: it may be an ethical imperative. Ethical guidelines in all mental health disciplines share language that mandates providers to act in a patient's best interests while practicing within the boundaries of their professional competence. These ethical considerations should have an impact on every facet of a provider's clinical practice, including the decision to refer patients for medical evaluation.We believe that an obligation to refer is especially true for mental health providers with no medical training, who, understandably, do not have the requisite knowledge of common medical illnesses that masquerade as psychological problems. Consequently, the risk of their missing general medical illnesses during client assessment and ongoing treatment is high. Thus nonmedical behavioral health specialists might view medical referral as an ethical obligation to promote patient welfare and to prevent potential harm. The obligation to refer may be particularly applicable in situations that involve patients who have newly diagnosed or treatment-resistant mental disorders. The obligation is considerably less when a person is being treated solely for work-related or relationship issues.Psychiatrists and other medically trained providers may have greater latitude in the decision to refer for medical evaluation. However, medically trained mental health care providers should be ever mindful of the limits of their general medical competence and allow patient safety concerns to guide their referral decisions. Indeed, viewing the referral process as a clinical decision shaped by strong ethical concerns will help all clinicians to be more mindful of their abiding obligation to promote and protect the welfare of those who come under their care.North Florida-South Georgia Veterans Health System, Gainesville, FloridaUniversity of Florida College of Medicine, Jacksonville FiguresReferencesCited byDetailsCited ByNone Volume 61Issue 1 January, 2010Pages 3-3PSYCHIATRIC SERVICES January 2010 Volume 61 Number 1 Metrics PDF download History Published online 1 January 2010 Published in print 1 January 2010

Referral for Medical Evaluation: An Ethical Obligation?

Back to table of contents Next article Taking IssueFull AccessReferral for Medical Evaluation: An Ethical Obligation?Glenn D. Grace Ph.D., M.S.,Richard C. Christensen M.D., M.A.,Glenn D. Grace Ph.D., M.S.Search for more papers by this author,Richard C. Christensen M.D., M.A.Search for more papers by this author,Published Online:1 Jan 2010https://doi.org/10.1176/ps.2010.61.1.3AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Many behavioral health providers might believe that medical illnesses capable of producing psychological disorders are rare and unlikely to be a significant issue in mental health treatment. However, studies of both inpatient and outpatient clinical samples indicate that an alarming number of patients have unrecognized medical illnesses that directly cause or contribute to their psychiatric symptoms. If these illnesses are unrecognized and untreated, dire health consequences may result.From a best-practices perspective, it can be argued that a collaborative model of integrated primary and behavioral health care affords patients the greatest opportunity for optimal treatment and recovery. However, most systems that deliver behavioral health care are separated from primary care services by systemic and ideological chasms. Nevertheless, if a somatic illness is suspected to be an underlying cause of a psychiatric disorder, the mental health provider bears the responsibility of referring the patient for a more thorough medical evaluation.We contend that referring all psychiatric patients with newly diagnosed and treatment-refractory disorders for a medical evaluation is more than good practice: it may be an ethical imperative. Ethical guidelines in all mental health disciplines share language that mandates providers to act in a patient's best interests while practicing within the boundaries of their professional competence. These ethical considerations should have an impact on every facet of a provider's clinical practice, including the decision to refer patients for medical evaluation.We believe that an obligation to refer is especially true for mental health providers with no medical training, who, understandably, do not have the requisite knowledge of common medical illnesses that masquerade as psychological problems. Consequently, the risk of their missing general medical illnesses during client assessment and ongoing treatment is high. Thus nonmedical behavioral health specialists might view medical referral as an ethical obligation to promote patient welfare and to prevent potential harm. The obligation to refer may be particularly applicable in situations that involve patients who have newly diagnosed or treatment-resistant mental disorders. The obligation is considerably less when a person is being treated solely for work-related or relationship issues.Psychiatrists and other medically trained providers may have greater latitude in the decision to refer for medical evaluation. However, medically trained mental health care providers should be ever mindful of the limits of their general medical competence and allow patient safety concerns to guide their referral decisions. Indeed, viewing the referral process as a clinical decision shaped by strong ethical concerns will help all clinicians to be more mindful of their abiding obligation to promote and protect the welfare of those who come under their care.North Florida-South Georgia Veterans Health System, Gainesville, FloridaUniversity of Florida College of Medicine, Jacksonville FiguresReferencesCited byDetailsCited byNone Volume 61Issue 1 January, 2010Pages 3-3PSYCHIATRIC SERVICES January 2010 Volume 61 Number 1 Metrics PDF download History Published online 1 January 2010 Published in print 1 January 2010

Improvement and Recovery From Suicidal and Self-Destructive Phenomena in Treatment-Refractory Disorders

Long-term data about recovery from suicidal and self-destructive phenomena are limited. We examined these phenomena in a naturalistic, follow-along study of 226 adults with treatment-refractory disorders admitted at the Austen Riggs Center. Follow-along interviews systematically rated suicidal ideation, suicide attempts, self-mutilation, and other self-destructive phenomena. We identified vital status in 98.7%, finding 1 death by suicide. Among 79 who made at least 1 suicide attempt in the 6 months before admission, 61 (77.2%) were estimated to be free of suicidal acts by a median of 7.18 years. Self-mutilation and other self-destructive phenomena showed slightly longer times to recovery. Among 156 individuals with suicidal ideation, 79 (50.6%) attained sustained recovery at a median of 8.69 years. On average 2.9 to 5.2 years were required from the last observed self-destructive event to attain sustained recovery. Most participants showed significant improvement in suicidal phenomena, whereas between 50.6% and 77.2% attained sustained recoveries.

Electrodes in the brain: Some anthropological and ethical aspects of deep brain stimulation

In the following text, medical, anthropological and ethical issues of deep brain stimulation, a medical technology in which electrodes implanted in the human brain electrically influence specified brain regions, will be discussed. After a brief account of the deep brain stimulation procedure and its chances and risks, anthropological and ethical aspects of the approach will be discussed. These relate to the reversibility of the procedure and to the patient?s capacity to control the effects it exerts in the brain, to modifications and fluctuations in a person?s character traits and individuality brought about by neurostim ulation, an d to the range of legitim ate, adequate uses of the deep brain stimulation approach. The paper concludes that deep brain stimulation should be confined to therapeutic contexts and to severe, otherwise treatment-refractory disorders in which the aim is to norm alize brain fun ctioning. A part from this, it sh ould not be used to m odify a person?s individ ual character traits and behaviour or to enhance human traits.

An Open Trial of Naltrexone in the Treatment of Depersonalization Disorder

Depersonalization disorder (DPD) remains one of the few disorders in modern psychiatry for which no treatments are established that are even partially effective, whether pharmacological or psychotherapeutic. Depersonalization disorder is a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition dissociative disorder characterized by a pervasive subjective sense of unreality and detachment with intact reality testing. Two recent controlled medication trials, one with lamotrigine and one with fluoxetine, failed to show efficacy. There is some evidence for dysregulation of endogenous opioid systems in depersonalization, and a few studies have suggested that opioid antagonists may have efficacy in the treatment of dissociation and depersonalization symptoms. In this prospective open treatment trial, 14 subjects were recruited and treated with naltrexone for 6 weeks to a maximum dose of 100 mg/d (first 7 subjects) or 10 weeks to a maximum dose of 250 mg/d (next 7 subjects). Mean naltrexone dose was 120 mg/d. There was an average 30% reduction of symptoms with treatment, as measured by 3 validated dissociation scales. Three patients were very much improved, and 1 patient was much improved with naltrexone treatment. These findings are potentially promising in a highly treatment-refractory disorder for which no treatment guidelines exist and warrant a randomized controlled trial.

Personality and Symptom Change in Treatment-Refractory Inpatients: Evaluation of the Phase Model of Change Using Rorschach,TAT, and DSM-IV Axis V

In this study, we examined global treatment outcomes during 16 months of intensive, psychodynamic treatment for 77 inpatients suffering from treatment-refractory disorders. Hypotheses based on the phase model of treatment change (Howard, Lueger, Maling, & Martinovich, 1993; Howard, Moras, Brill, Martinovich, & Lutz, 1996) were supported in the study results. Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) Axis V scales assessing behavioral functioning demonstrated large and medium effect size change, whereas stable, enduring personality functioning assessed by psychoanalytic Rorschach scales and the Social Cognition and Object Relations Scale (Westen, 1995) for the Thematic Apperception Test (Murray, 1943) demonstrated small and medium effect size change. We also report assessment of reliable change index and clinical significance. The ecological validity of Rorschach measures is supported by significant validity coefficients (in the hypothesized directions) between implicit measures of personality functioning and behavioral ratings.

Day hospital versus out-patient care for psychiatric disorders.

This review considers the use of day hospitals as an alternative to out-patient care. Three types of day hospital are covered by the review: 'day treatment programmes', 'day care centres' and 'transitional' day hospitals. Day treatment programmes offer more intense treatment for patients who have failed to respond to out-patient care (usually patients with affective or personality disorders). Day care centres offer structured support to patients with long-term severe mental disorders (mainly schizophrenia), who would otherwise be treated in the out-patient clinic. Transitional day hospitals offer time-limited care to patients who have just been discharged from in-patient care. The review had three objectives. First, to assess the effectiveness of day treatment programmes versus out-patient care for people with treatment-refractory disorders. Second, to assess the effectiveness of day care centres versus out-patient care for people with severe long term disorders. Third, to assess the effectiveness of transitional day hospital care for people who had just been discharged from hospital. We searched the Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (January 1966 to December 2000), EMBASE (1980 to December 2000), CINAHL (1982 to December 2000), Psyc LIT (1966 to December 2000), and the reference lists of articles. Researchers were approached to identify unpublished studies. Randomised controlled trials comparing day hospital care (including day treatment programme, day care centre, and transitional day hospital) against out-patient care. Studies were ineligible if a majority of participants were under 18 or over 65, or who had a primary diagnosis of substance abuse or organic brain disorder. Data were extracted independently by two reviewers and cross-checked. Relative risks and 95% confidence intervals (CI) were calculated for dichotomous data. Weighted or standardised means were calculated for continuous data. There was evidence from one trial suggesting that day treatment programmes were superior to continuing out-patient care in terms of improving psychiatric symptoms. There was no evidence that day treatment programmes were better or worse than out-patient care on any other clinical or social outcome variable, or on costs. There was no evidence that day care centres were better or worse than out-patient care on any clinical or social outcome variable. There were some inconclusive data on costs suggesting that day care centres might be more expensive than out-patient care. There was evidence from one trial suggesting that transitional day hospital care was superior to out-patient care in keeping patients engaged in treatment, however there was insufficient evidence to judge whether it was better or worse on any other clinical or social outcome variable, or on costs. There is only limited evidence to justify the provision of day treatment programmes and transitional day hospital care, and no evidence to support the provision of day care centres.

Obsessive Compulsive Disorder: Serotonin and Beyond

Summary: OCD was considered a rare, treatment refractory disorder of psychological origin, up until 20 years ago. Research in the last two decades has altered the perspectives regarding OCD. It is now clear that OCD is a prevalent disorder—about 2% of the population suffer from OCD—and that it is amenable both to psychological (cognitive-behavioural approach) and pharmacological intervention (with serotonergic medication). The biochemical and neuroanatomical (the frontal basal-thalamo cortical circuit) pathophysiology of OCD is also beginning to emerge.OCD is unique with regards to its specific response to serotonergic medication that blocks reuptake. Clomiprimine, fluoxetine, fluvoxemine, paroxetine, sertraline and citalopram were all found to be effective treatments for OCD based on large, multicentre, double-blind, placebo-controlled studies. As only serotonergic medications appear to be effective in OCD, the serotonergic hypothesis has been formulated and tested. Indeed, pharmacological challenges with specific serotonin agonists such as mCPP and sumatriptan, which were associated with transient exacerbation of OCD symptoms, are in line with the specific role of 5HT in the pathogenesis of OCD. However, this serotonergic hypothesis, while necessary, is not sufficient. It is clear that the dopaminergic and autoimmune mechanism are also implicated in the pathogenesis of OCD.Further studies are required to understand the relevance of the serotonergic and non-serotonergic systems in OCD, and to highlight the various possible subtypes of this intriguing disorder.

Treatment of schizoaffective disorder and schizophrenia with mood symptoms.

Patients with concurrent schizophrenic and mood symptoms are often treated with antipsychotics plus antidepressant or thymoleptic drugs. The authors review the literature on treatment of two overlapping groups of patients: those with schizoaffective disorder and those with schizophrenia and concurrent mood symptoms. MEDLINE searches (from 1976 onward) were undertaken to identify treatment studies of both groups, and references in these reports were checked. Selection of studies for review was based on the use of specified diagnostic criteria and of parallel-group, double-blind design (or, where few such studies addressed a particular issue, large open studies). A total of 18 treatment studies of schizoaffective disorder and 15 of schizophrenia with mood symptoms were selected for review. For acute exacerbations of schizoaffective disorder or of schizophrenia with mood symptoms, antipsychotics appeared to be as effective as combination treatments, and there was some evidence for superior efficacy of atypical antipsychotics. There was evidence supporting adjunctive antidepressant treatment for schizophrenic and schizoaffective patients who develop a major depressive syndrome after remission of acute psychosis, but there were mixed results for treatment of subsyndromal depression. There was little evidence to support adjunctive lithium for depressive symptoms and no evidence concerning its use for manic symptoms in patients with schizophrenia. Empirical data suggest that both groups of patients are best treated by optimizing antipsychotic treatment and that atypical antipsychotics may prove to be most effective. Adjunctive antidepressants may be useful for patients with major depression who are not acutely ill. Careful longitudinal assessment is required to ensure identification of primary mood disorders.

Current concepts in the pharmacological treatment of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and often disabling disease. OCD is characterised by intrusive, unwanted and persistently recurring mental events (obsessions) that usually evoke discomfort or anxiety, and/or repetitive ritualistic behaviours (compulsions) that are aimed at reducing discomfort and anxiety. However, the compulsions succeed only in achieving transient relief, followed by a growing sense of pressure. 10 years ago, OCD was considered a rare and treatment-refractory disorder. Recent well designed studies document a lifetime prevalence rate for OCD of more than 2% in the general population. The outlook for patients with OCD has changed in the last decade, with many well controlled studies showing that OCD patients respond to specific behavioural and pharmacological treatments. The specific form of behavioural therapy is in vivo exposure coupled with response prevention. Only serotonin reuptake inhibitors, such as clomipramine, fluoxetine and fluvoxamine, are effective in the treatment of both depressed and not depressed OCD patients. Fluoxetine and fluvoxamine lack the anticholinergic side effects of clomipramine and, thus, provide an alternative treatment for patients who cannot tolerate clomipramine. Other nonserotonergic antidepressants (tricyclics and monoamine oxidase inhibitors) and anxiolytic agents have not been found to be consistently effective in this disorder. Insufficient data on the efficacy of neuroleptics and their potentially irreversible side effects limit their use in OCD patients. Behavioural and the pharmacological treatment are complementary, and a combination of the 2 therapies is apparently more effective than either modality alone.

Drug treatment of obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) traditionally has been considered a rare, treatment refractory disorder of psychological origin. However, OCD appears to be much more common than was previously believed. Moreover, in recent years controlled studies demonstrated that clomipramine is more effective than placebo and than other tricyclics for reducing obsessive-compulsive symptoms. Although it has been suggested that clomipramine was effective in treating obsessive-compulsive symptoms by an antidepressant mechanism, the majority of the controlled studies found that its antiobsessional effects occurred whether the patient was depressed or not. The apparent specificity of clomipramine, and, to some extent, newer serotonin selective antidepressants, suggests a serotonergic role in the psychobiology of OCD.