Jacqueline E. Muller

Quetiapine augmentation of SRIs in treatment refractory obsessive-compulsive disorder: a double-blind, randomised, placebo-controlled study [ISRCTN83050762]

BackgroundAlthough serotonin reuptake inhibitors are effective in the treatment of OCD, many patients fail to respond to these agents. Growing evidence from open-label and placebo-controlled trials suggests a role for augmentation of SRIs with atypical antipsychotics in OCD. Quetiapine is generally well tolerated and previous open-label data has produced mixed results in OCD and additional controlled data is needed.MethodsWe undertook a double-blind, randomised, parallel-group, flexible-dose, placebo-controlled study of quetiapine augmentation in subjects who had responded inadequately to open-label treatment with an SRI for 12 weeks. Following informed consent and screening, forty-two subjects were randomised to either placebo or quetiapine for six weeks.ResultsThere was significant improvement from baseline to endpoint on the Yale-Brown Obsessive-Compulsive Scale in both the quetiapine and placebo groups (quetiapine, n = 20, p < 0.0001; placebo, n = 21, p = 0.001) with 40% (n = 8) of quetiapine and 47.6% (n = 10) of placebo treated subjects being classified as responders. Quetiapine did not demonstrate a significant benefit over placebo at the end of the six-week treatment period (p = .636). Similarly quetiapine failed to separate from placebo in the subgroup of subjects (n = 10) with co-morbid tics. Quetiapine was generally well tolerated.ConclusionsIn this study, quetiapine augmentation was no more effective than placebo augmentation of SRIs. A number of limitations in study design make comparisons with previous studies in this area difficult and probably contributed to our negative findings. Future work in this important clinical area should address these limitations.

Cognitive-affective neuroscience of somatization disorder and functional somatic syndromes: Reconceptualizing the triad of depression-anxiety-somatic symptoms

Somatization disorder is a somatoform disorder that overlaps with a number of functional somatic syndromes and has high comorbidity with major depression and anxiety disorders. Proposals have been made for revising the category of somatoform disorders, for simplifying the criteria for somatization disorder, and for emphasizing the unitary nature of the functional somatic syndromes in future classifications. A review of the cognitive-affective neuroscience of somatization disorder and related conditions suggests that overlapping psychobiological mechanisms mediate depression, anxiety, and somatization symptoms. Particular genes and environments may contribute to determining whether symptoms are predominantly depressive, anxious, or somatic, and there are perhaps also overlaps and distinctions in the distal evolutionary mechanisms that produce these symptoms.

Escitalopram in the treatment of multisomatoform disorder: A double-blind, placebo-controlled trial

Despite the prevalence of multisomatoform disorder (MSD), there are few controlled trials of its pharmacotherapy. The aim of this study was to compare the efficacy and safety of escitalopram (10–20 mg/day) with that of placebo in treating patients with MSD over a 12-week period. Fifty-one outpatients aged from 18 to 65 years, with multiple medically unexplained symptoms, were recruited. The primary efficacy measure was a change on the Patient Health Questionnaire-15 scores from baseline to endpoint. Secondary efficacy endpoints included the Clinical Global Impression-Improvement score, the psychic and somatic subscales of the Hamilton Anxiety Scale, Montgomery–Asberg Depression Rating Scale, the Visual Analogue Pain Rating Scale, the Scale for the Assessment of Illness Behaviour and the Sheehan Disability Scale. On the primary analysis of covariance, escitalopram-treated patients had significantly greater reductions in Patient Health Questionnaire scores (P<0.0001) compared with placebo at week 12. Significant separation from placebo occurred from week 6 onwards. Escitalopram was superior to placebo on all secondary outcome endpoints, with the exception of the Scale for the Assessment of Illness Behaviour. The medication was well tolerated. In conclusion, in this 12-week, randomized, placebo-controlled study, escitalopram (10–20 mg/day) was both effective and well tolerated in the treatment of patients with MSD. Compared with placebo, escitalopram was associated with lower symptom scores, increased response and remission rates, and improved functioning.

Social anxiety disorder : current treatment recommendations.

Social anxiety disorder (SAD) is a prevalent and disabling disorder associated with significant co-morbidity. An increased awareness of SAD over the past two decades has given impetus to advances in the pharmacotherapeutic and psychotherapeutic treatment options for this disorder. On the basis of consistent data from randomised controlled trials, present consensus supports the use of SSRIs as the first-line treatment in generalised SAD, partly because of established short-and long-term efficacy in this disorder, evidence for safety and tolerability, and ability to treat co-morbid conditions. There is more recent evidence that venlafaxine XR (extended release) may also be considered a first-line treatment in SAD. Second-line treatments include MAOIs (e.g. phenelzine) and reversible inhibitors of monoamine oxidase A (e.g. moclobemide), while some benzodiazepines and antiepileptics (e.g. clonazepam and pregabalin) may also be useful. Over the past two decades, cognitive behavioural therapies for SAD have gained increasing empirical support. The optimal approach to the management of treatment-refractory SAD patients requires additional study.

Positive and negative symptoms in affected sib pairs with schizophrenia: implications for genetic studies in an African Xhosa sample.

Careful phenotyping and the identification of subtypes of schizophrenia can contribute significantly to the success of genetic studies in schizophrenia. The phenomenology of schizophrenia in affected sib pairs has been well-described in Caucasian populations, however a paucity of data exists for African populations. This study therefore investigated symptom dimensions in a sizeable group of affected Xhosa sib pairs as a means of evaluating the role of shared familial factors in the psychosis of schizophrenia. Five hundred and thirteen participants were interviewed with the Diagnostic Interview for Genetic Studies (DIGS), which included the Schedules for the Assessment of Negative and Positive symptoms (SANS/SAPS). One hundred and four sib pairs were then extracted (N = 208) for analysis of concordance for lifetime psychotic symptoms and an exploratory factor analysis of the SANS/SAPS. Concordance analysis of life-time symptoms indicated a significant concordance for olfactory hallucinations, persecutory delusions, jealousy, somatic, reference and control delusions as well as thought insertion and withdrawal. The factor analysis of the global scores of the SAPS and SANS revealed a five factor best-fit model and accounted for 92.5% of variance. The factors included a negative symptom factor, a positive symptom factor, a positive thought disorder and a bizarre behaviour component. The core symptomatology of schizophrenia in this sib pair sample was similar to that reported in Caucasian populations with the exception of higher rates of auditory hallucinations and delusions of persecution. In summary therefore; although the factor analysis only supported the concept of the universality of psychotic symptoms in schizophrenia, the concordance analysis of these symptoms did reveal hallucinations as well as delusions of control as possible candidates relevant for future research into genotype-phenotype relationships.

Reboxetine and citalopram in panic disorder: A single-blind, cross-over, flexible-dose pilot study

Both noradrenergic and serotonergic systems have been implicated in the pathophysiology of panic disorder. The advent of selective serotonin (5-HT) reuptake inhibitors (SSRIs) (e.g. citalopram) and, more recently, selective noradrenergic (NA) reuptake inhibitors (NRIs) (e.g. reboxetine) has provided potentially important avenues of treatment for the disorder. To date, the comparative efficacy of selective NA and 5-HT reuptake inhibitors for panic disorder remains unresolved. Nineteen patients with panic disorder were randomized in a single-blind, cross-over design to either citalopram or reboxetine for 8 weeks and after a 2-week washout were switched to the other study drug. At week 18, seven of 13 patients (54%) in the intent-to-treat sample responded to reboxetine and nine of 11 patients responded to citalopram (82%). Both citalopram and reboxetine led to significant improvements in panic attack severity with no apparent between-drug differences in efficacy. However, citalopram demonstrated superior efficacy in treating depressive symptoms. One non-responder to citalopram responded to reboxetine and three non-responders to reboxetine responded to citalopram. Although SSRIs are viewed as a first-line treatment for panic disorder, these results suggest that a NA agent such as reboxetine may also have a role. These data also suggest an advantage for citalopram in treating comorbid depressive symptoms, although some patients may respond preferentially to an SSRI and other patients to an NRI.

Obsessive compulsive disorder - Prevalence in Xhosa-speaking schizophrenia patients

Obsessive compulsive disorder (OCD) has been reported in up to 31% of schizophrenia sufferers. This study evaluated the presence of OCD in a Xhosa-speaking schizophrenia group. Xhosa patients (N = 509, including 100 sibships) with schizophrenia were recruited from hospital and community settings. The patients underwent a structured clinical interview for the presence of lifetime co-morbid schizophrenia and OCD. Only 3 patients (0.5%) fulfilled criteria for OCD. No concordance for OCD was noted in the sibship group. Our findings differ from those in other parts of the world, and if replicated, might suggest unique protective environmental or genetic factors for OCD in certain ethnic groups.

Depression and anxiety in multisomatoform disorder: Prevalence and clinical predictors in primary care

OBJECTIVE Multisomatoform disorder (MSD) is characterised by > or = 3 medically inexplicable, troublesome physical symptoms, together with a > or = 2-year history of somatisation. The aim of this study was to evaluate the prevalence of depressive and anxiety disorders in a South African sample MSD, and to compare demographic and clinical outcomes in those patients with and without co-morbidity. METHODS Fifty-one adult outpatients with MSD were recruited from primary care clinics in the Cape Town metropolitan area. Participants were assessed for the presence of co-morbid depressive and anxiety disorders using the Mini Neuropsychiatric Interview-Plus (MINI-Plus). Outcomes included somatic symptom severity, disability, reported sick days and health care visits, pain experience, patient satisfaction with health services, and clinician-experienced difficulty. RESULTS A current co-morbid depressive disorder was present in 29.4% (N = 15) of patients, and a current co-morbid anxiety disorder in 52.9% (N = 27). MSD patients with a co-morbid depressive disorder (current or lifetime) had significantly higher physical symptom counts, greater functional impairment, higher unemployment rates, more clinician-reported difficulties, and more dissatisfaction with health care services than those without the disorder. A larger number of co-morbid disorders was associated with greater overall disability. CONCLUSION High rates of co-morbid depressive and anxiety disorders were present in a South African sample of primary care patients with MSD. Not all patients had co-morbidity, which is consistent with the view that MSD should be viewed as an independent disorder. However, co-morbid depressive disorders were associated with increased symptom severity and functional impairment, consistent with previous reports from developing countries, emphasising the importance of comorbidity in MSD.

Use of traditional treatment methods in a Xhosa schizophrenia population.

To the Editor: Although most countries promote westernised medical practices as the norm, different forms of traditional healing have always formed a component of health care. In keeping with traditional beliefs that illness should be viewed in terms of magical, social, physical and religious parameters, traditional healers divide illnesses into those of natural causation and those of traditional cultural aetiology peculiar to the specific culture.

A case of Ifufunyane : a Xhosa culture-bound syndrome

Clinicians and patients frequently have a different understanding and interpretation of the nature of an illness. While many reasons for these discrepancies can be postulated, differences in sociocultural background often play an important role—especially in the field of psychiatry. At our tertiary psychiatric hospital in South Africa, where standard Western teachings are followed, clinicians are often confronted by patients who have a markedly different interpretation of their psychiatric symptoms compared with the clinician’s perspective. For instance, “ifufunyane” (plural “amafufunyana”), a ritualized”“possession state,” often thought to result from witchcraft, is frequently reported by South African (Xhosa) patients with psychosis (including schizophrenia) and their families.