Yehuda Sasson

Alternation learning in obsessive-compulsive disorder

The Wisconsin Card Sorting Test (WCST) and an alternation learning task were administered to 15 women with obsessive-compulsive disorder (OCD) and 15 age-, sex-, education-, and intelligence-matched healthy controls. OCD patients were significantly slower on the WCST as compared to the controls. Their performance on the alternation learning task was impaired relative to the control group, though this difference was diminished when we used education as a covariate. We found a significant positive correlation between performance on the alternation task and severity of symptoms in the OCD group. Performance of similar alternation tasks is impaired by damage to the orbitofrontal cortex in nonhuman primates. Therefore the data presented support the hypothesis of orbitofrontal cortex dysfunction in OCD.

Pindolol augmentation in treatment-resistant obsessive compulsive disorder: a double-blind placebo controlled trial.

OBJECTIVE To evaluate the efficacy of pindolol augmentation in treatment-resistant obsessive compulsive disorder (OCD) patients who were unsuccessfully treated with serotonin reuptake inhibitors. METHOD Fourteen treatment-resistant OCD patients were treated with paroxetine for 17.4+/-2.1 weeks up to 60 mg/d after they failed at least two other serotonin reuptake inhibitor trials. The patients, who did not respond to open-label paroxetine treatment, were assigned to a double-blind, placebo-controlled pindolol (2.5 mgx3/d) augmentation. All the subjects were evaluated biweekly for a six-week period with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAM-Anx), and Montgomery Asberg Depression Rating Scale (MADRS). Data was analyzed by paired t-test, and ANOVA with repeated measures. RESULTS Pindolol augmentation to paroxetine (n=8) as compared to placebo augmentation (n=6), was associated with a significant (P<0.01) improvement in Y-BOCS as measured by paired t-test after the fourth week of the treatment and by ANOVA with repeated measures (df: 4.9, f: 3,3, P<0.006). Although no significant differences were found between placebo and pindolol groups on HAM-Anx and MADRS, a trend for improvement in the pindolol group was noted. CONCLUSIONS The results of our study demonstrated that pindolol may augment the therapeutic effect of paroxetine in treatment-resistant OCD patients.

Serotonergic Dissection of Obsessive Compulsive Symptoms: A Challenge Study with m-Chlorophenylpiperazine and Sumatriptan

We have conducted a pharmacological challenge experiment in 10 medication-free obsessive compulsive (OC) disorder (OCD) patients. We used a placebo-controlled paradigm for m-chlorophenylpiperazine (mCPP) and sumatriptan challenges. Endocrine, physiological and behavioral variables were assessed at baseline and over a 3-hour period after the challenge. Both cortisol and prolactin were significantly elevated in OCD patients following mCPP administration. Both mCPP and sumatriptan caused significant OC symptom exacerbation with the response to sumatriptan being more robust. We conclude that the 5-HT1Dβ receptor may play a role in the pathophysiology of OCD.

Treatment of severe, drug resistant obsessive compulsive disorder with the 5HT1D agonist sumatriptan

The serotonergic system has been implicated in both the aetiology and pharmacological treatment of obsessive compulsive disorder. In pharmacological challenge tests, mCPP, a 5-HT agonist, with an affinity for 5HT2C as well as 5HT1A and 5HT1D receptors, was associated with a transient exacerbation of obsessive compulsive symptoms. Chronic administration of mCPP was found to bring about some relief of these symptoms. Sumatriptan is an antimigraine agent, which interacts most potently with 5HT1D receptors. In the cases to be presented, we report the effects of chronic administration of Sumatriptan to three severe, treatment resistant, OCD patients. Following chronic administration of sumatriptan, these patients, who have been resistant to any former pharmacological treatment, responded with an improvement in their depression and a modest reduction in their obsessive compulsive symptoms.

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.

Posttraumatic obsessive–compulsive disorder: A case series

This report documents emerging posttraumatic obsessive-compulsive disorder in 13 Israeli military veterans diagnosed with both obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD), for whom the onset of OCD was clearly associated with the trauma. Data presented include four detailed case reports that delineate relations between symptomatology in the two disorders. Clinical and theoretical implications of these data are discussed.

Bipolar comorbidity: from diagnostic dilemmas to therapeutic challenge

Comorbidity in bipolar disorder is the rule rather than the exception more than 60% of bipolar patients have a comorbid diagnosis and is associated with a mixed affective or dysphoric state; high rates of suicidality; less favourable response to lithium and poorer overall outcome. There is convincing evidence that rates of substance use and anxiety disorders are higher among patients with bipolar disorder compared to their rates in the general population. The interaction between anxiety disorders and substance use goes both ways: patients with bipolar disorder have a higher rate of substance use and anxiety disorder, and vice versa. Bipolar disorder is also associated with borderline personality disorder and ADHD, and to a lesser extent with weight gain. As more than 40% of bipolar patients have anxiety disorder, it is indicated that while diagnosing bipolar patients, systematic enquiry about different anxiety disorders is called for. This also presents a therapeutic challenge, since agents that effectively treat anxiety disorders are associated with the risk of induced mania. Therefore, the treating psychiatrist needs to carefully evaluate the potential benefit of treating the anxiety against the potential cost of inducing a manic episode. A possible solution would be to use, when possible, a non-pharmacological intervention, such as a cognitivebehavioural approach. Alternately, it is suggested that the clinician attempts to ensure that the patient receives adequate treatment with mood stabilizers before slowly and carefully attempting the addition of anti-anxiety compounds with a relatively lower risk of mania induction (e.g. SSRIs compared to TCAs).

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.

The pathogenesis and treatment of obsessive-compulsive disorder

The outlook for patients with obsessive-compulsive disorder (OCD) began to change in the early 1980s with the introduction of clomipramine (CMI), a serotonergic antidepressant. The observation that only drugs with a serotonergic profile are effective in OCD has been the basis for the serotonergic hypothesis of OCD. The serotonin-selective reuptake inhibitors are effective alternatives for CMI and can be used when the patient cannot use or tolerate CMI. In this review, we examine the pathophysiology of OCD, based on drug response profile, peripheral markers of serotonergic function, pharmacologic challenge studies, and neuroimaging. We also consider the medications found to be effective in OCD, the length of treatment, with special regard for maintenance therapy, and such issues as the approach for the treatment-resistant patient, augmentation strategies, and nonpharmacological treatments.

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.