Treating anxiety without SSRIs
Are SSRI side effects a problem for your patient with generalized anxiety disorder? Here are some options to consider—and others to avoid.
Venlafaxine has some of the same adverse effects as the SSRIs, however; commonly reported side effects include nausea, dizziness, and somnolence,12,16 as well as a significant incidence of sexual side effects.14,17 For this reason, venlafaxine would not be the best choice for Brad. It might, however, be an option for a patient who is bothered by sedation or weight gain caused by SSRIs.
Anticonvulsants: A newer option for anxiety
Anticonvulsants have been used only recently to treat anxiety disorders—an indication for which this class of drugs has not received approval. The mechanism of action appears to involve suppression of neuronally activated “fear circuits” in the amygdala and hippocampus. These circuits are part of the autonomic output that occurs when someone initially experiences fear, and when he or she reexperiences the fear in a nonthreatening setting. Periodic or chronic overactivation of these circuits may lead to panic attacks, GAD, and other anxiety disorders.18
Anticonvulsants suppress neuronal activation through a variety of mechanisms, including gamma-aminobutyric acid stimulation (valproate), sodium channel blockade (carbamazepine, phenytoin), and calcium channel blockade (pregabalin). Although a variety of anticonvulsants have been tested as a treatment for GAD, pregabalin is the only 1 that multiple RCTs have found to be effective.19-22 In an RCT comparing pregabalin, lorazepam, and placebo, both pregabalin and lorazepam decreased anxiety scores significantly more than placebo. Pregabalin was better tolerated than lorazepam and had the added benefit of not being associated with withdrawal effects upon discontinuation of the drug. In addition, pregabalin showed efficacy compared with placebo in as little as 1 week.22
In another RCT comparing pregabalin, venlafaxine, and placebo, Montgomery et al showed that both pregabalin and venlafaxine were superior to placebo.23 Pregabalin had a faster onset of action than venlafaxine (1 vs 2 weeks) and was better tolerated.
Doses of pregabalin used in clinical trials ranged from 150 mg to 600 mg daily, given in divided doses.24 In clinical practice, physicians are advised to start at the lower dose and titrate upward until either an effective dosage is reached or side effects become bothersome.
Common side effects of pregabalin include dizziness (8%-45%), somnolence (4%-28%), weight gain (up to 16%), and edema (up to 16%.) Thrombocytopenia occurs in 3% of patients; other blood dyscrasias are rare.25 Laboratory monitoring is not routinely indicated, and neither sexual side effects nor gastrointestinal disturbances are commonly reported.25
With evidence indicating that GAD is a chronic, recurrent disease,26 long-term efficacy is important. One RCT found that longterm use of pregabalin (24 weeks) maintained remission of symptoms more effectively than placebo.27
The combination of fast onset of action, high efficacy, and lack of sexual side effects makes pregabalin an attractive drug for the treatment of GAD, especially for patients who cannot tolerate SSRIs. However, cost may be a consideration. Unlike SSRIs, pregabalin is not available as a generic. At a discount retailer such as Costco, the per-pill cost of pregabalin 150 mg (typically taken twice a day) is $2.45; in contrast, paroxetine 20 mg (generally taken only once daily) is 40 cents per pill. In addition, pregabalin is a class V controlled substance, and little is known about its long-term effects.
CASE 1 Pregabalin makes sense for Brad. After discussing SSRI alternatives with Brad, he decides to switch to pregabalin, despite the higher cost. He makes an appointment for the following month. At that visit, you’re pleased to see that Brad is feeling better and happy with the treatment choice he has made. Your next GAD patient, however, is a more difficult case.
CASE 2 Janet W, a 60-year-old patient whom you “inherited” from a former partner, has been taking alprazolam 1 mg tid for many years for “excessive nervousness.” She frequently complains about lack of energy and weight gain, but resists any suggestion that she discontinue alprazolam. “I can’t function without something to calm my nerves,” Janet says.
Benzodiazepines as a “bridge”
Benzodiazepines have long been established as effective in treating anxiety symptoms. Because of their fast onset of action, drugs in this class are often used as a “bridging strategy,” to give rapid relief from symptoms while another medication, typically an SSRI, is started and titrated.
A 2005 meta-analysis comparing benzodiazepines with placebo for short-term treatment of GAD showed the drugs to be superior to placebo in reducing anxiety symptoms. Patient satisfaction with benzodiazepines was high, as evidenced by a significantly lower dropout rate among those in the benzodiazepine group (20.5%), compared with the placebo group (30.2%).28 Typical side effects are somnolence and weight gain.
