The serotonin reuptake inhibitors (SRIs), including clomipramine, fluvoxamine, fluoxetine, sertraline, and paroxetine, have been approved by the U.S. Food and Drug Administration for the treatment of adults with obsessive-compulsive disorder; three of these (clomipramine, fluvoxamine, and sertraline) have been approved for treatment of children and adolescents. Clomipramine and the selective serotonin reuptake inhibitors (SSRIs) are first-line agents. However, 40 to 60 percent of patients with obsessive-compulsive disorder do not respond to adequate treatment trials with SRIs, and agents that alter serotonin receptors and other neurotransmitter systems, such as dopamine, norepinephrine, and second-messenger systems, may play a role in treatment. Treatment options for patients who do not respond to SRIs include switching, augmentation, or novel-agent strategies. Up to two-thirds of patients with obsessive-compulsive disorder have comorbid psychiatric disorders, which may present a challenge in pharmacologic treatment. Major depressive disorder is the most common comorbid condition. Nonpharmacologic invasive techniques may play a role in refractory cases of obsessive-compulsive disorder, but further research is warranted.
Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line pharmacological agents in treating obsessive-compulsive disorder (OCD). Appropriate treatment for OCD also involves cognitive behavioural therapy (CBT), including exposure and response prevention. As there is a time delay in seeing full therapeutic response, and not all patients tolerate SSRIs, there remains an unmet need for additional treatment approaches in OCD. In addition, most responders report only a partial reduction in symptoms. Clonazepam has demonstrated effectiveness in several preliminary reports in treating OCD. Twenty-seven patients with OCD were entered into a 10 week, double-blind, parallel design trial of clonazepam vs. placebo. Overall, only 3 out of 25 patients who had >/= 1 rating on clonazepam/placebo were judged to be treatment responders, by scoring a 1 (very much improved) or 2 (much improved) on the CGI improvement scale. Responders included 2 of 9 in the placebo group and 1 of 16 in the clonazepam group. No significant difference was found between clonazepam and placebo groups on responder/non responder status (Chi(2 )=1.39, df =1,24, p=0.238), nor on change in YBOCS, Ham-A, Ham-D or NIMH scales from beginning to last evaluation carried forward. These findings suggest that clonazepam is not effective as monotherapy in treating OCD. Its effectiveness in specific subgroups of OCD patients with co-morbid anxiety disorders or as an augmentation strategy added to SSRIs remains to be determined.
Autism is characterized by social deficits, communication and language impairments, narrow restricted interests, repetitive behaviors, inattention, and hyperactivity. While selective serotonin reuptake inhibitors have demonstrated efficacy in treating core symptoms of autism, norepinephrine reuptake inhibitors have demonstrated efficacy in symptoms of attention-deficit hyperactivity disorder (ADHD). An open, retrospective clinical study with venlafaxine evaluated its effect on core symptoms of autism as well as associated features of ADHD. Ten consecutive subjects meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for an autism spectrum disorder were treated with venlafaxine, initiated at 12.5 mg per day and adjusted on a flexible basis. Six of 10 completers were judged to be sustained treatment responders, by scoring 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions improvement scale. Venlafaxine was effective in low dosages (mean, 24.37 mg/day; range, 6.25 to 50 mg/day) and was well tolerated. Improvement was noted in repetitive behaviors and restricted interests, social deficits, communication and language function, inattention, and hyperactivity. Controlled treatment trials with venlafaxine are warranted in autism spectrum disorders.
Results of this pilot study support the efficacious use of duloxetine in comorbid IBS and GAD. Participants reported significant reductions in IBS components, as well as improvement in GAD.
Neurological soft-sign abnormalities have been implicated in obsessive-compulsive disorder (OCD). This first comprehensive data analysis evaluated the association between baseline neurological soft signs and treatment response in 117 OCD patients treated with controlled-release fluvoxamine in a double-blind placebo-controlled trial. Total and right-sided soft signs for the responders and the nonresponders did not differ significantly. Left-sided visuospatial soft signs were significantly increased in treatment nonresponders compared to responders. These subtle neurological abnormalities may implicate a potential subgroup of OCD patients with poorer treatment response. This may have treatment implications and therefore serve as a screening tool in OCD.
Objective:Body dysmorphic disorder (BDD), a preoccupation with imagined ugliness, is a disabling condition that seems to respond preferentially to selective serotonin reuptake inhibitors. This open-label trial examines venlafaxine's efficacy in BDD and is the first known study of this serotonin-norepinephrine reuptake inhibitor in BDD.Methods:A total of 17 BDD patients 16–65 years of age entered and 11 completed a 12–16 week open-label trial of venlafaxine. Participants were treated with venlafaxine until a therapeutic dose (minimum of 150 mg/day) was reached and then maintained at that dose for 8 weeks. Key outcome measures were the Yale-Brown Obsessive-Compulsive Scale Modified for Body Dysmorphic Disorder and Clinical Global Impressions-Improvement scale.Results:Venlafaxine was found to be effective in lessening the specific symptoms and global severity of BDD. Paired t-tests were used to compare baseline and final ratings on the Yale-Brown Obsessive-Compulsive Scale Modified for Body Dysmorphic Disorder total, obsessions, and compulsions scores; by this measure venlafaxine significantly reduced BDD symptoms overall (P=.012), as well as obsessions (P=.034) and compulsions specifically (P=.021). A single sample t-test, comparing final Clinical Global Impressions-Improvement scale ratings to “no change” (score: 4) found significant improvement following treatment.Conclusion:Venlafaxine may be an effective treatment for BDD, including both obsessive and compulsive symptoms. Controlled research on venlafaxine in BDD is recommended.
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