Q. Can smokers who have generalized anxiety safely take Wellbutrin? I've read so many conflicting accounts. Some say it greatly increases anxiety; some say it helps. Is it reasonable to add something like Ativan to the Wellbutrin?

A. I haven't seen (and couldn't locate) any studies specifically looking at bupropion [Wellbutrin-SR] for smoking cessation in patients with co-morbid generalized anxiety disorder [GAD]; however, I have no reason to believe that GAD is a contraindication to use of this agent.

Sustained-release bupropion (bupropion SR) at the recommended dosage of 150 mg twice daily may be associated with side effects such as insomnia, headache, dry mouth, nausea and anxiety. However, insomnia and anxiety may also be due to nicotine withdrawal. When you look at rates of bupropion side effects versus a placebo control, only insomnia and dry mouth occur significantly more frequently with bupropion SR than with placebo (HJ Aubin, Drugs 2002;62 Suppl 2:45-52).

But these studies have not looked at co-morbid nicotine dependence and GAD, to my knowledge. However, there is at least one study (Sampablo Lauro et al, Arch Bronconeumol 2002 Aug;38(8):351-5) examining the relationship of smoking cessation and the presence of anxious or depressive symptoms, in patients using bupropion. Somewhat surprisingly, patients who responded better to treatment with bupropion after 6 months of follow-up were those with higher anxiety scores on the hospital anxiety and depression scale (HADS).

Depression levels influenced outcome only during the first month. Finally, Hertzberg et al (J Clin Psychopharmacol 2001 Feb;21(1):94-8) studied the use of bupropion-SR in patients with post-traumatic stress disorder (PTSD), in which generalized anxiety is often part of the overall picture. Eighty percent of patients receiving bupropion SR successfully stopped smoking by the end of week 2, and 6 (60%) of these 10 maintained smoking cessation at the study endpoint (week 12).

At the 6-month follow-up, 40% of the patients (4 of 10) who received bupropion SR maintained smoking cessation. One (20%) of the five patients who received placebo stopped smoking and maintained smoking cessation at the 6-month follow-up. Bupropion SR was generally well-tolerated in combination with other psychotropic medications. The authors concluded that "Bupropion SR may be effective in helping patients who desire to quit smoking and who also have a concomitant anxiety disorder, such as PTSD."

So, in short, I have no reason to believe that GAD patients could not tolerate bupropion-SR. If the patient did have a problem with increased anxiety, I might consider buspirone [BuSpar] rather than a benzodiazepine, given the tendency to substance abuse among some smokers; however, a very brief trial on a benzodiazepine (7-14 days) would not be out of the question, absent a history of alcohol or non-nicotine substance abuse. [Also, it will usually take 1-2 weeks for buspirone to kick in, as you no doubt know].

Other Resources:

• More Questions on Anxiety Disorders

July 2003

Disclaimer Back to Ask the Expert