Five Treatments for Smoking Cessation Compared
What is the best way to help someone quit smoking? A recent trial compared the most popular over-the-counter and prescription treatments to answer this question. 1,504 participants were randomly assigned to one of six conditions: a nicotine patch, a nicotine lozenge, a patch + lozenge, bupropion, bupropion + lozenge, or placebo. In addition, all participants had six 10 to 20 minute counseling sessions with a supervised bachelor’s-level clinician. The lozenge was taken for 12 weeks, while other treatments were given for eight weeks. The main outcome variable was the seven day abstinence rate, as confirmed by expired carbon monoxide levels during study visits. After eight weeks, three of the treatments were statistically significantly more effective than placebo (which yielded a 30.2% abstinence rate): the patch alone (44.7%), the patch + lozenge (53.6%), and bupropion + lozenge (50.4%). At six months post quit (four months after treatment was discontinued), only patch + lozenge was more effective than placebo (40.1% vs. 22.2%). All the treatments were well-tolerated; only four participants withdrew due to medication-related adverse events (Piper ME et al., Arch Gen Psychiatry 2009;66:1253–1262).
TCPR’s Take: While these results may seem discouraging, the authors used a conservative statistical approach to adjust for multiple comparisons. When they reanalyzed the results using a more liberal technique, they found that all five treatments led to higher quit rates than placebo. Nonetheless, the take-home message from this and other clinical trials is that combining the patch with some form of ad-lib nicotine replacement (such as the nicotine lozenge, gum, or spray) is particularly effective. Unfortunately, Chantix (varenicline) was not tested in this study because it had not yet been approved by the FDA. A recent open-label randomized trial found Chantix more effective than the nicotine patch alone (without ad-lib nicotine replacement), with Chantix yielding a 55.9% abstinence rate after 12 weeks vs. 43.2% for the patch (Aubin HJ, et al., Thorax 2008;63:717–24). However, the patch was used alone without ad-lib nicotine replacement, and the Chantix advantage was no longer significant after one year.
Does Adding Psychotherapy Help Patients With Resistant Depression?
Patients who don’t respond well to medication for depression are often referred for psychotherapy. But there has been little evidence that this actually works. A recent trial attempted to assess whether this method could help patients. Researchers assigned a group of 808 patients, all of whom had been chronically depressed for more than two years, to one of five antidepressants based on an algorithm (possibilities included sertraline, escitalopram, bupropion, venlafaxine, or mirtazapine). Those who did not respond to the medication by 12 weeks (491 patients total) had their medication regimens optimized according to a predefined algorithm. In this algorithm (referred to as “MEDS” in the paper) patients with no response to the first medication were switched to a different antidepressant, while those with a partial response received augmentation with either bupropion or venlafaxine. These patients were then randomly assigned to one of three conditions: MEDS alone, MEDS plus supportive therapy, or MEDS plus a type of cognitive behavioral therapy. Outcomes were measured after 12 weeks on the Hamilton depression scale, and there was no significant difference in either remission rates (average of 15%) or partial response rates (22.5%). Thus, surprisingly, adding psychotherapy offered no notable advantages over medication by itself (Kocsis JH et al., Arch Gen Psychiatry 2009;66:1178–1188).
TCPR’s Take: Before we conclude that adding psychotherapy does not help patients with treatment resistant depression, it is important to note that the “medication only” patients received more clinician contact than is typical. These patients had, on average, 5.2 visits with their psychiatrists over the course of the 12-week study, a visit frequency of nearly every two weeks. These frequent visits could have boosted response to medication. Also, the patients in this study were apparently skeptical of the benefits of psychotherapy—the authors reported that participants often “required considerable convincing” that psychotherapy was valuable. Finally, these results were specific to treatment-resistant depression; a prior meta-analysis found that adding psychotherapy at the start of depression treatment is associated with better outcomes than medication alone (Pampallona S et al., Arch Gen Psychiatry 2004;61:71–719).
Combined Treatment Works Better Than Risperidone Alone for PDD
Combining medication and behavioral therapy leads to better outcomes for children with pervasive developmental disorders (PDDs), according to a recent study. Pervasive developmental disorder (PDD) is an umbrella diagnostic category that includes autism, Asperger’s syndrome, and pervasive developmental disorder-not otherwise specified (PDD-NOS). (For a basic review of PDD, see “Citalopram Not Effective for Autism in Children,” TCPR July/August 2009.) Clinicians often use risperidone to treat the aggression, tantrums and other behavioral issues that are common with PDD patients. This study was the first to look at whether adding behavioral treatment to medication would improve outcomes. One hundred and twenty four children, ages 4 through 13, with PDDs and significant irritable behavior were randomly assigned either risperidone or risperidone + behavioral therapy. Risperidone was dosed according to weight and titrated to a potential maximum dose of 3.5 mg/day. Up to 17 sessions of highly structured behavioral therapy were offered by trained master’s or doctoral level therapists over 24 weeks. During therapy, patients’ parents were taught positive reinforcement, compliance, functional skills, and social skills. At the end of the study, the combined treatment group had statistically significantly higher rates of improvement on the Home Situations Questionnaire (which measures problem behaviors); and on rating scales of irritability, hyperactivity/noncompliance; and on one of two scales of repetitive behavior. There was no difference between treatments on social withdrawal or inappropriate speech. The most notable side effect was weight gain; mean BMI increased from 67th percentile to 84th percentile over 24 weeks. The combined group’s medication dose was 14% lower than the risperidone-only group, indicating that adding behavior therapy might allow physicians to moderate antipsychotic dosing, with a potential improvement in side effects (Aman MG et al., J Am Acad Child Adolesc Psychiatry 2009;48:1143–1154).
TCPR’s Take: Adding behavioral treatment to risperidone decreases irritability in children with PDDs more than using risperidone alone. The effect is moderate, so it is a judgment call whether the extra time and expense that therapy requires is worth it in all cases. The researchers plan to make the manual and other behavioral treatment materials available for public use, which should help to disseminate the method more broadly.