Side effect expert Prakash Masand once observed that “the difference between a good clinician and a great clinician is that a great clinician is better at managing side effects.”

In this spirit, the current issue of TCR endeavors to answer your most burning questions about minimizing side effects, with a focus on antidepressants, both because these are the most commonly used psychotropics, and because we can’t cover everything in 8 pages.

Research indicates that side effects are a bigger problem for our patients that we might think. One intriguing study looked at 627 patients prescribed Prozac or Paxil in the Northern California Kaiser Permanente health care system. Over a third of these patients discontinued their SSRI within 3 months, 43% within 6 months. Listed below are the most complained- about side effects in this population: Drowsiness/Fatigue, 41%; Dry mouth, 32%; Insomnia, 26%; Anxiety, 24%; Sexual Dysfunction, 24%; Headache, 23%; Dizziness, 23%; Nausea, 17%; Weight gain, 14%; and Diarrhea, 14%. These figures are useful because they represent more real-world side effect estimates than you’ll find in the PDR.

A third of patients discontinue SSRIs within 3 Months

These clever researchers went a step beyond just asking patients about side effects. In an effort to give us some guidance on what to tell our patients as we hand them a prescription, they asked respondents what they recalled their doctors having told them when treatment began. Those who were instructed to stay on their medication for at least 6 months were three times more likely to continue their meds. Now that’s a pretty easy intervention! On the other hand, going over a list of possible side effects with patients did not affect compliance, but it did lead to the perception of more adverse events. Perhaps we should reconsider how much information our patients really need at the outset.

So, how should we manage the common antidepressant side effects?

1. Fatigue. First, rule out a sleep problem as the cause of fatigue. In true antidepressant fatigue, patients say they sleep more than enough at night, yet they feel like they could fall asleep at any point throughout the day. As a remedy, it’s hard to beat Ritalin or Dexedrine 5- 10 mg Q AM. You may want to start with a longer-acting stimulant, such as Concerta 18 mg or Adderall 10 mg QAM. Stimulant dosages required for AD-fatigue are generally lower than typical ADHD doses. If you’re wary of substance abuse, try Provigil (modafinil), starting at 100 mg QAM, and titrating up as high as 400.


2. Insomnia. You probably know plenty about treating insomnia, since we eventually address this problem in the vast majority of our patients. The usual pitfalls here are failing to rule out sleep apnea (ask if their partner notices snoring and gasping for air) and restless leg syndrome (ask if they thrash around in bed and if they notice “creepy crawly” sensations in their legs). Otherwise, every clinician has their own favorite algorithm for insomnia, often starting with “sleep hygiene tips” (but let’s face it, once they reach your office, these are unlikely to work), then moving to the non-addictive medications (Benadryl 25- 50 mg., Trazodone 25-50, melatonin 1-3, Elavil 10-20, Doxepin 50, Neurontin 100-300), then moving to the semiaddictive newer non-benzos (Ambien 10-20, Sonata 10-20), then to the benzos (Restoril 15-30, Ativan 0.5-1), and finally to heavy-hitting atypicals (Seroquel 25-50, Zyprexa 2.5-5).


3. Sexual Dysfunction. See this month’s article devoted to this topic.


4. Weight gain. Weight gain seems most likely to be a problem with Paxil or Remeron, but we’ve all seen patients gain weight on the other agents as well. By far the best tactic is prescribing Wellbutrin SR 300-400 mg QDay, either in combination or switching to it as monotherapy. Placebo-controlled studies show that non-depressed patients lose about 8% of body weight after a year on this regimen; depressed patients lose about half this much. Topomax (topiramate) dosed at 100-150 mg QDay also works for weight loss, but beware of its cognitive side effects, which have earned it the nickname “Dopamax” among savvy psychopharmacologists.


5. Apathy Syndrome. A pretty common (seen in 20-30%) and only recently talked about side effect of SSRIs and SNRIs primarily, apathy syndrome is sometimes tricky to diagnose. In addition to the dopaminergic antidotes recommended by Dr. Pies in this month’s Q&A, one case report has endorsed the seemingly nonsensical approach of using Zyprexa, a dopamine blocker, to treat a putatively hypodopaminergic state. In this open label study, 16 of 21 patients with SSRIinduced apathy improved on an average dose of 5.4 mg QD of Zyprexa (2). Go figure.


6. Excessive sweating. This is a big Effexor side effect although it is also seen with the SSRIs. Use Hytrin (terazosin) 1-2 mg QD (approved for hypertension and benign prostatic hypertrophy), or Ditropan (oxybutynin) 5 mg QD-BID (approved for spastic bladder).


7. Dry Mouth. This turns out to be more than a minor nuisance, since it can lead to dental problems due to a decrease in the usual antibacterial activity of saliva. There are over-the-counter liquid saliva products (eg., “Saliva Substitute” and “Salivant”) which are twice-daily mouth rinses that can relieve the sensation of dryness temporarily. Make sure your patients know about the higher risk of dental caries, and encourage frequent dental check-ups as well as the use of fluoride rinses.


8. Constipation. Yes, it happens with the newer agents as well as the tricyclics. Don’t jump to medications; rather, follow the lead of primary care doctors who advise increasing fiber intake to bulk up the stool (“eat more fresh fruits and vegetables, salads, and brown rice; eat less white bread and white rice”), increase water intake to improve stool transit (“drink at least three big glasses of water a day, in addition to any other liquids you drink—coffee does not count as a liquid!”), and exercise more, which stimulates bowel motility. If these fail, a gentle stool softener like Colace is fine (OTC—usual dose 100 mg TID as needed) or even Miralax, which is an intensively advertised prescription-only combination stool softener/laxative taken as a powder mixed with juice once a day. The strong bowel stimulants, like Milk of Magnesia, Senekot, and Dulcolax, should only be used short term because of the risk of paradoxical worsening of constipation with chronic use.

TCR VERDICT:
Advice for Patients: Stay the Course