TCPR: Dr. Pies, how would you recommend that psychiatrists approach the management of medication-related side effects?

DR. PIES: I think the most important thing for psychiatrists is to think strategically and not automatically jump to using another medication to treat a medication side effect. My own strategy is to think about the five R's: Reduce, Reschedule, Reformulate, Rescue and Replace. The first thing to ask is whether you can simply reduce the dose of the medication. And while that is often helpful, it risks reducing the efficacy of the medication so it is a double-edged sword. The next thing is to consider rescheduling the treatment. For example, as dating medication can be given at bedtime so that the patient just sleeps through the side effect of drowsiness. Another way of rescheduling is to split the dose so that instead of giving 600 mg of drug A once a day, you are giving 300 twice a day. For some side effects, like hypotension, that may work fairly well. On the other hand, depending on the side effect, sometimes giving all of the med- ication at once can be helpful. So, for example, with lithium-related polyuria, if you give all of the lithium at bedtime, it seems to reduce the polyuria. “Reformulate” refers to using alternatives such as enteric-coated formulations or “sprinkles,” often to reduce GI side effects — for example, Depakote instead of Depakene, which is fairly common practice. “Rescue” refers to adding something else that counteracts the drug side effects, such as benztropine (Cogentin) for extrapyramidal side effects of first-generation antipsychotics. And, finally, replace, where we decide that we have to change horses in order to get rid of a side effect.

TCPR: I’d like to go through some of the more common side effects of psychotropics and discuss some specific ways to manage these. Let’s start with that bugaboo, dry mouth.

DR. PIES: Dry mouth is usually an anticholinergic side effect, and aside from switching to a less anticholinergic agent, what I have found useful is to add bethanechol 25 mg b.i.d. This raises the availability of acetylcholine and can work quite well for a lot of people. And it may also help with some of the other anticholinergic effects that they may have, such as urinary retention or constipation. 

TCPR: And what about the side effects of bethanechol itself?

DR.PIES: Usually it is pretty well tolerated. Theoretically, you can over shoot and put the person into sort of cholinergi cover drive in which case they are going to complain now of salivation and diarrhea instead of dry mouth and constipation. But I have never seen that happen.

TCPR: And what about the opposite type of side effect, excessive sweating, which can occur with most SSRIs and SNRIs.

DR. PIES: Sweating (or “hyperhidrosis”) is generally a serotonergic side effect and so one common strategy is to use cyproheptadine, which is a serotonin antagonist. Other agents that are used are benztropine (Cogentin) and clonidine. And then one interesting approach, which may be a little counterintuitive, is to add a small amount of mirtazapine (Remeron). The reason for this is that mirtazapine, which works by stimulating the 5-HT1 receptor and blocking presynaptic autoreceptors, actually blocks two of the serotonin receptors that we think are involved in a lot of serotonergic side effects: 5-HT2 and 5-HT3.

TCPR: Let’s move on now to weight gain, which is a big concern these days with the antipsychotics, but is also common with some antidepressants.

DR. PIES: Well, the first thing I recommend is to “prepare the battlefield,” even before your patient begins taking the potentially weight- gaining medication. This means encouraging them to exercise more, reduce sugary drinks, reduce fat in their diet, etc. That can be a very difficult message to convey, but there are studies showing that getting patients involved in Weight Watchers and programs like that can be helpful. Reducing the dose of the antipsychotic doesn’t seem to help that much with weight gain, at least in my experience. So we are often looking at either changing the medication to something less likely to promote weight gain (for example, switching from olanzapine to ziprasidone or aripiprazole), or rescue strategies, of which there are several: sibutramine (Meridia), topiramate (Topamax), nizatidine (an H2 blocker), orlistat, metformin and amantadine.

TCPR: Orlistat is on a lot patients’ minds, because it was just approved as an over the counter agent, under the name “Alli.”