Seth Kindler

Current Concepts in the Pharmacological Treatment of Obsessive-Compulsive Disorder

SummaryObsessive-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 de-signed 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.

Olfactory Sensitivity in Major Depressive Disorder and Obsessive Compulsive Disorder

Olfactory sensitivity to two odorants, isoamyl acetate and androsterone, was assessed in 14 obsessive compulsive disorder (OCD) patients, nine major depressive disorder (MDD) patients, and 16 sex- and age-matched healthy controls. Tests were performed during a drug-free period, and 3 and 6 weeks after initiation of antidepressant drug therapy. No difference in olfactory sensitivity, to either odorant, was found between OCD patients and controls at any time. In MDD patients, a significant increase in the sensitivity to isoamyl acetate was observed 6 weeks after initiation of treatment, compared to controls.

Hormone responses to fenfluramine and placebo challenge in endogenous depression.

Plasma prolactin and cortisol levels after oral administration of d-l fenfluramine hydrochloride (60 mg) and placebo were examined in 24 endogenously depressed patients and 21 age- and sex-matched normal control subjects in a randomized, double-blind study. Prolactin levels were significantly increased by fenfluramine in both groups, but the response was significantly blunted in the depressed patients compared with the controls. This effect was partially dependent upon elevated baseline cortisol levels in the depressed group and was also influenced by a history of weight loss. Plasma cortisol levels were not increased by fenfluramine in either group. These findings confirm previous reports and suggest that patients with endogenous major depression are characterized by central serotonergic hyporesponsivity. The need to account for baseline effects on hormonal responses to putative serotonergic agents is supported by the findings; however, these effects appear to be less striking when endogenicity is a prominent clinical feature of the depressive syndrome. The apparently complex influence of weight loss on prolactin response to serotonergic challenge remains to be clarified as well as the role played by the bioavailability of the challenge drug and its metabolite.

Emergence of kleptomania during treatment for depression with serotonin selective reuptake inhibitors.

Kleptomania, one of the rare impulse-control disorders, is characterized by an irresistible impulse to steal objects not needed for personal use or monetary value. There is a comorbidity between mood disorders, eating disorders, anxiety disorders, personality disorders, and kleptomania. Several recent case reports have suggested that serotonin reuptake inhibitors could be effective in the treatment of obsessive-compulsive spectrum disorders and specifically in kleptomania. We describe three depressed patients who paradoxically experienced kleptomanic behavior during treatment with serotonin selective reuptake inhibitors.

The treatment of comorbid premature ejaculation and panic disorder with fluoxetine.

Premature ejaculation is a common sexual disturbance among men. Both open-label and double-blind studies have demonstrated the effectiveness of serotonergic medications for this disorder. These studies support the hypothesis that the serotonergic system has an important role in the modulation of sexual response, especially attainment of orgasm. Serotonergic dysfunction also has been linked to the pathogenesis of panic disorder. Several studies have demonstrated the efficacy of serotonergic drugs in this disorder. The purpose of the present study was to examine the efficacy of fluoxetine, a serotonin selective reuptake inhibitor for the treatment of comorbid premature ejaculation and panic disorder, in 10 men in an open-label design. The patients were given 20 mg of fluoxetine for 8 weeks of the study. Parameters pertaining to sexual function and measures of anxiety were examined. Improvement of premature ejaculation was noted as of week 2 of the study, whereas measures of panic and sexual satisfaction became statistically significant only as of week 4. Further studies with larger samples and longer periods of follow-up are needed in order to determine the usefulness of fluoxetine for the treatment of comorbid premature ejaculation and panic disorder.

Differences in cognitions during chest pain of patients with panic disorder and ischemic heart disease.

A significant number of patients with chest pains who undergo coronary angiography (20–30%) have normal coronary arteries. Up to 50% of this group are eventually diagnosed as Panic Disorder and most continue to complain of their symptoms, in spite of the normal coronary angiogram. We hypothesized that the cognitions of panic disorder subjects on presentation with chest pain would differ from those of patients suffering from true angina pectoris.

Anxiogenic effects of Sumatriptan in panic disorder: A double-blind, placebo-controlled study

BACKGROUND Several lines of evidence point to serotonergic abnormalities in patients with panic disorder (PD). Our goal was to further examine central serotonergic function in panic patients using autonomic and subjective responses to the postsynaptic serotonin 5-HT1D receptor agonist Sumatriptan. METHOD Using a double-blind, randomized, placebo-controlled design, we assessed autonomic and subjective responses to oral Sumatriptan (100 mg) and placebo in 15 patients with PD, free of medication. Subjective responses were measured using the Hamilton Anxiety Rating Scale (HAM-A), National Institute of Mental Health Anxiety Scale (NIMHA), a modified version of the Panic Symptom Inventory (PI), Hamilton Depression Rating Scale (HAM-D), and Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS PD patients exhibited significantly enhanced autonomic and subjective responses following challenge with Sumatriptan. We observed an increased pulse rate and augmentation of various parameters measured on different anxiety scales. A constant inclination of aggravation of the measured parameters was detected during the hour post challenge. CONCLUSION Oral administration of Sumatriptan, a 5-HT1D agonist, has been associated with an anxiogenic effect in PD patients.

Pharmacological Manipulation of Seizure Duration: A New Direction in ECT Technology

The use of caffeine sodium benzoate to prolong electroconvulsive therapy (ECT)-induced seizures was first prompted by preclinical studies in our department on the effect of electroconvulsive shock (ECS) on adenosine receptors of the A1 subtype. Newman et al.1 found an increase in maximal binding (Bmax) of [3H]cyclohexyladenosine to these receptors in rat cerebral cortex after repeated ECS. Because A1 adenosine receptors have been linked to anticonvulsant effects,2 enhancement of their sensitivity or number could play a role in the increase in seizure threshold and reduction in seizure duration, which are frequent concomitants of an ECT course. Methylxanthines inhibit A1, adenosine receptors and increase seizure duration3; administration of caffeine prior to ECT therefore seemed a plausible method for enhancing the efficacy of the treatment. The intervention would be of greatest potential importance in patients whose seizure threshold rises during ECT to an extent that results in short, clinically ineffective seizures.

Resistant Depression: Clinical Characteristics and Response to Treatment

The terms “resistant” or “refractory” depression imply a state of illness that can potentially respond to treatment. The further implication is that conventional therapeutic interventions have been applied at dosages that are adequate and for a sufficient duration to elicit the desired response. In individuals whose depression is labeled “resistant,” this situation is not always the case. Furthermore, there is no universally agreed on definition of the term with respect to the number of modalities that should have received an adequate trial. It is also not clear which treatments are regarded as “conventional” and which are not. Whether, for example, electroconvulsive therapy (ECT) falls in the category of conventional therapies is a case in point.