Prednisone augmentation in treatment-resistant depression with fatigue and hypocortisolaemia: a case series.

Abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis have long been implicated in major depression with hypercortisolaemia reported in typical depression and hypocortisolaemia in some studies of atypical depression. We report on the use of prednisone in treatment-resistant depressed patients with reduced plasma cortisol concentrations. Six patients with treatment-resistant major depression were found to complain of severe fatigue, consistent with major depression, atypical subtype, and to demonstrate low plasma cortisol levels. Prednisone 7.5 mg daily was added to the antidepressant regime. Five of six patients demonstrated significant improvement in depression on prednisone augmentation of antidepressant therapy. Although hypercortisolaemia has been implicated in some patients with depression, our findings suggest that hypocortisolaemia may also play a role in some subtypes of this disorder. In treatment-resistant depressed patients with fatigue and hypocortisolaemia, prednisone augmentation may be useful.

Neuropharmacology of paradoxic weight gain with selective serotonin reuptake inhibitors.

It has been suggested that weight gain associated with tricyclic antidepressants (TCA) reflect actions on dopamine (DA) and histamine receptors. However, a definitive cause is purely assumptive given the nonselective pharmacology of these agents. The selective serotonin reuptake inhibitors (SSRIs), as well as agents like dexfenfluramine (DFF), have emphasized the pivotal role of serotonin (5HT) in reducing carbohydrate (CHO) intake, and have provided a more selective tool with which to study appetite regulation. It would be expected that all SSRIs should exert a similar anorectic action. However, recent reports provide evidence to the contrary. Despite their claimed selectivity, SSRIs still interact, either directly or indirectly, with various critical neurotransmitter systems. In addition, although the anorectic action of fluoxetine (FLX) is well recognized, long-term follow-up studies in depressed patients and in obese nondepressed patients reveal that its weight-reducing effects are transient, even leading to a gain in body weight. Similarly, paroxetine (PRX) and citalopram (CTP) have also been associated with weight gain. These latter observations are unexpected because PRX and CTP are highly potent and selective SSRIs. A neuropharmacologic rationale for the apparent paradoxic effects of SSRIs on appetite not a review of neuronal regulation of appetite is presented in this article. As with the regulation of feeding, paradoxic weight gain observed with SSRIs appears to rest on the interaction of 5HT with multiple mechanisms, with the extent of weight gain observed being dependent on subtle, yet important pharmacologic differences within the group. Finally, the neurobiology of depressive illness itself, and of recovery from it, is a major contributing factor to individual response to these drugs.

Moclobemide and fluoxetine for panic disorder. International Panic Disorder Study Group.

An international, multicentre, double blind parallel group study compared the tolerability and efficacy of moclobemide with the selective serotonin reuptake inhibitor (SSRI) fluoxetine for panic disorder. SSRIs have been shown effective for panic. The target dose of moclobemide was 450 mg and of fluoxetine was 20 mg. There were two consecutive studies. An eight week study of acute adverse events, tolerability and efficacy was followed by a long-term extension study to 1 year. The efficacy data showed no significant difference between moclobemide and fluoxetine. Both had acute efficacy, with 63% moclobemide and 70% fluoxetine patients (ns) panic free at 8 weeks. Both agents were well tolerated to 8 weeks, but moclobemide had fewer severe adverse events (5) than fluoxetine (9). There were no severe adverse events in the extension phase with either drug, and almost all patients completing 1 year extension treatment (moclobemide 61 patients, fluoxetine 65) were much or very much improved. These data suggest moclobemide and fluoxetine are tolerated and effective for both acute panic treatment and maintenance therapy.

Panic disorder following torture by suffocation is associated with predominantly respiratory symptoms.

BACKGROUND: We previously reported that in panic disorder a history of near-suffocation is associated with predominantly respiratory panic attacks. It might be hypothesized that the near-suffocation experienced in certain kinds of torture is also associated with the development of predominantly respiratory panic attacks. METHODS: A sample of patients who had experienced torture (N = 14) was drawn from an Anxiety Disorders Clinic in South Africa. Subjects were questioned about symptoms of panic disorder, posttraumatic stress disorder and depression. RESULTS: Patients with a history of torture by suffocation were more likely than other patients to complain of predominantly respiratory symptoms during panic attacks. These patients also demonstrated higher levels of depressive symptoms. CONCLUSIONS: While various interpretations of the data can be made, it is possible that torture by suffocation is associated with a specific symptomatic profile. Were such an association to be replicated, this would perhaps support the suffocation alarm hypothesis of panic disorder and provide evidence that specific environmental factors play a role in the development of this alarm.

Trichobezoars in trichotillomania: case report and literature overview.

OBJECTIVE: Although trichobezoars are well described in the surgical literature, there is relatively little in the psychiatric literature on them. This study aims to focus the attention of readers on trichobezoars by means of a case report and an overview of the literature. METHOD: We present a case of a patient with trichotillomania and a trichobezoar, including psychiatric management. We also briefly review the relevant literature. RESULTS: Hair-pulling significantly improved in response to treatment with the selective serotonin reuptake inhibitor fluoxetine and supportive psychotherapy. CONCLUSIONS: The medical and psychiatric sequelae of trichotillomania should not be underestimated. Pharmacotherapy may be play a useful role in some patients with this disorder.

Use of the selective serotonin reuptake inhibitor citalopram in the treatment of generalized social phobia.

BACKGROUND: There is increasing evidence that social phobia responds to treatment with selective serotonin reuptake inhibitors (SSRIs). However, the efficacy of citalopram, the most selective of the SSRIs, in social phobia has not been well documented. METHODS: Citalopram was used on an open-label naturalistic basis in 22 social phobia patients presenting for treatment (40 mg daily for 12 weeks). Patients were rated with the Liebowitz Social Anxiety Scale and the Clinical Global Impressions (CGI) scale. RESULTS: Ratings on the Liebowitz Social Anxiety Scale and the CGI were significantly improved after treatment. A total of 86% of patients were responders at week 12. LIMITATION: Open, uncontrolled study. CONCLUSIONS: Citalopram appears to be effective in the treatment of social phobia. A controlled trial is warranted to confirm these data. The role of serotonin in social phobia deserves further study.

Is olfactory reference syndrome an obsessive-compulsive spectrum disorder?: two cases and a discussion.

A number of disorders characterized by intrusive repetitive symptoms and varying degrees of insight may overlap phenomenologically and neurobiologically with obsessive-compulsive disorder (OCD). There is a question as to whether olfactory reference syndrome, a disorder characterized by persistent preoccupations about body odor accompanied by shame and embarrassment, is also an OCD spectrum disorder. Two cases of olfactory reference syndrome, with accompanying phenomenological and neurobiological data, are presented in order to discuss the possible overlap with OCD. A number of phenomenological and neurobiological features in these patients were at least partially reminiscent of OCD. In particular, despite having poor insight, both patients demonstrated significant improvement upon treatment with a serotonin reuptake inhibitor.

Hyperresponsivity to nicotinic acid challenge in generalized social phobia: a pilot study.

Although blushing is an almost pathognomonic feature of social phobia, little is known about the neurobiology of blushing in this disorder. Nicotinic acid (100 mg), a vasodilator that may induce flushing, was administered to six male patients with generalized social phobia and to six healthy male controls. Compared with controls, patients demonstrated increased flushing, anxiety, autonomic activity, and temperature after nicotinic acid administration. Further controlled research is necessary to confirm and extend these pilot findings.

Association of panic disorder with a history of traumatic suffocation.

OBJECTIVE: An important recent hypothesis suggests that panic disorder results from a false suffocation alarm. However, the association of panic disorder with a history of traumatic suffocation experiences (e.g., near-drowning and near-choking) has not been well studied. This study examined whether a history of traumatic suffocation might be more common in patients with panic disorder who have predominantly respiratory symptoms. METHOD: Patients with panic disorder (N = 176) and psychiatric comparison subjects (N = 60) were questioned about a history of traumatic suffocation experiences. The panic disorder patients were classified as having predominantly respiratory, cardiovascular, occulovestibular, or gastrointestinal symptoms in order to determine a possible association between traumatic suffocation and symptom subtype. RESULTS: The frequency of traumatic suffocation was significantly higher among the panic disorder patients (19.3%) than among the comparison subjects (6.7%). Within the panic disorder group, patients with a history of traumatic suffocation were significantly more likely to exhibit predominantly respiratory symptoms and nocturnal panic attacks, while patients without such a history were significantly more likely to have predominantly cardiovascular symptoms, occulovestibular symptoms, and agoraphobia. CONCLUSIONS: There may be a specific association between panic disorder and a history of traumatic suffocation, and such a history in turn appears associated with predominantly respiratory symptoms and nocturnal panic attacks. Although additional studies are needed to confirm these data, a history of traumatic suffocation might be hypothesized to play a role in the etiology of panic disorder in some patients and may provide a useful window on understanding the psychobiology of this disorder.

Blushing and social phobia: a neuroethological speculation.

Blushing is a well-known but relatively poorly understood phenomenon. This paper reviews the phenomenology, neurobiology, and psychology of blushing. We argue that a neuroethological understanding of blushing provides a useful explanation of many aspects of normal blushing, and leads to a useful account of social phobia. More specifically, we argue that social phobia can be conceptualized in terms of an inappropriate appeasement display.

A neuro-evolutionary approach to the anxiety disorders.

BACKGROUND: Advances in our understanding of the anxiety disorders and in the application of evolutionary principles to medicine provide the possible basis for a neuro-evolutionary approach to these conditions. In this paper, initial steps taken towards such an approach are described. METHODS: Neuro-evolutionary accounts of each of the anxiety disorders have been offered. Notably, several of these accounts have suggested that particular anxiety disorders are mediated by specific brain-based false alarms. This paper reviews the strengths and weaknesses of such accounts. RESULTS: The false suffocation alarm of panic attack is the most fully elaborated of the neuro-evolutionary accounts of an anxiety disorder. However, viable neuro-evolutionary approaches have also been offered for other anxiety disorders, such as obsessive-compulsive disorder and social phobia. CONCLUSIONS: Further work is necessary to consolidate a neuro-evolutionary approach to the anxiety disorders. Although the theoretical basis for such an approach has become increasingly appealing over the last several years, this foundation requires supplementation by further empirical research.

Magnetic resonance brain imaging in women with obsessive-compulsive disorder and trichotillomania.

Magnetic resonance imaging of the brain was undertaken in women with obsessive-compulsive disorder (n = 13), trichotillomania (n = 17), and healthy controls (n = 12). Caudate volume and ventricular-brain ratio (VBR) (variables that have previously been highlighted as abnormal in studies of OCD) were compared in the three subject groups and were correlated with neuropsychological and neurological soft sign findings. No significant differences were found between women with OCD, trichotillomania and normal controls on caudate volume or VBR. Decreased left caudate volume was significantly correlated with impairment on neuropsychological testing and with increased neurological soft signs. The negative findings here may indicate that in women with OCD and related disorders structural brain abnormalities are less obvious or less common than in men with these conditions, or they may reflect inadequate sensitivity of the brain measures employed.

Buspirone is an effective augmenting agent of serotonin selective re-uptake inhibitors in severe treatment-refractory depression.

BACKGROUND: Buspirone has previously been reported to be effective in the augmentation of the antidepressant effect of serotonin selective re-uptake inhibitors (SSRIs) in depressed outpatients. We report on buspirone augmentation of SSRIs in severe treatment-refractory depression in inpatients. METHODS: A retrospective chart review was undertaken of patients diagnosed with DSM-III-R major depression and treated at our inpatient unit. All 14 patients had been given structured depression rating scales before and after addition of buspirone to a SSRI. RESULTS: Patients had previously failed multiple trials of antidepressants, often including lithium and/or thyroid augmentation, as well as, in 12 cases, electroconvulsive therapy. However, augmentation of an SSRI with buspirone led to a rapid and significant improvement in depression in 6 of 14 (43%) patients. CONCLUSION: Despite the limitations of the study design, our results support previous work suggesting the need for further controlled research on the use of buspirone in the augmentation of the antidepressant response to the SSRIs.

Risperidone augmentation of serotonin reuptake inhibitors in obsessive-compulsive and related disorders.

BACKGROUND: While serotonin is the neurotransmitter most commonly implicated in obsessive-compulsive and related disorders, there is also evidence for dopaminergic mediation of these conditions. Indeed, augmentation of serotonin reuptake inhibitors with the atypical neuroleptic risperidone has been suggested to be useful in obsessive-compulsive disorder (OCD). METHOD: Charts of all patients treated in our OCD clinic with the combination of a serotonin reuptake inhibitor and risperidone were reviewed. Demographic details of patients and clinical response to this pharmacotherapeutic strategy were tabulated. RESULTS: A series of patients with OCD (N = 8), trichotillomania (N = 5), and Tourette's syndrome (N = 3) who were refractory to treatment with serotonin reuptake inhibitors had received risperidone augmentation. In a number of cases, this strategy proved clinically effective. However, a minority of patients experienced significant adverse effects. CONCLUSION: Patients with OCD and related disorders are not infrequently refractory to treatment with serotonin reuptake inhibitors. Controlled trials of risperidone augmentation in such patients seem warranted. In particular, it is necessary to determine an appropriate dose range to minimize adverse effects.