Question. After five months of severe depression that was unresponsive to medication, I had ECT and came out of the depression. I was immediately started on Wellbutrin and Zoloft and have been on them for over a year now. The only atypical side effects I experienced were spontaneous myoclonic jerks and those are infrequent now. For the past two weeks, I awake early in the morning due to severe fine tremors of my hands and abdominal muscles. Any ideas about the cause? I am concerned because Wellbutrin isn’t approved for more than a year’s use.
Also, do you agree with my psychiatrist’s view that because of my depression’s severity and having a brother who committed suicide after life-long depression, I am going to be on some type of antidepressants for the remainder of my life?
Answer. Your symptoms are, indeed, puzzling! It is hard to posit some new drug or drug interaction as a cause of the muscle tremors, since you have been on the same medications at the same dose for a year. As you may know, serotonergic antidepressants (SSRIs) like sertraline [Zoloft] can occasionally cause tremors or other extrapyramidal reactions, perhaps as a result of decreased dopamine in certain brain regions. But the fact that you awaken with these symptoms, and are apparently relieved after taking your medication, suggests a more complicated mechanism.
In theory, it is possible that, overnight, your plasma levels of sertraline drop significantly, such that you actually get some mild withdrawal effects by morning; muscle twitching could be due to this, though it would be very atypical. It is theoretically possible that you are developing some kind of dyskinesia, related to the sertraline, and that you are actually masking it by taking your morning medications. The theory is that chronic dopaminergic blockade, due to the sertraline, leads to compensatory dopamine receptor hypersensitivity, with resultant muscle twitching or dyskinesia. Taking the medication in the morning might temporarily relieve this by reestablishing dopamine receptor blockade. All this, I want to emphasize, is very speculative on my part.
For the vast majority of patients taking SSRIs, no problems of the sort you describe ever develop, and even in animal models, the effects I’ve described (e.g., on dopamine) are still open to debate. I haven’t said anything about the bupropion [Wellbutrin], since the mechanism of action of Wellbutrin is not well understood; however, it probably has effects on both norepinephrine and dopamine, in high enough doses. There may well be pharmacokinetic interactions between sertraline and bupropion.
Could there be some third factor – say, a change in your caffeine intake, or some over-the-counter medication, or a recent infection – that could account for the change in the past two weeks? At this point, it might be instructive (if your doctor concurs) to try changing the timing of one or both of your medications, sequentially. For example, if you are taking the Zoloft in the a.m., try taking it at bed time, or vice versa. If you are taking the Wellbutrin in the a.m. and afternoon, try shifting it to afternoon and late evening, etc. But frankly, since this is so recent a phenomenon, the most prudent course may be simply to wait another two weeks and see if it persists.
You might also want to have the plasma level of your bupropion checked, along with its metabolite, hydroxy-bupropion. High levels of the metabolite have been associated with various neurologic side effects – though it’s hard to account for why this would now be a problem. Dosage reduction of one or both medications could also be a reasonable maneuver that might shed light on the problem. This would need to be weighed against the risk of recurrent depression, of course, and all these issues should be discussed with your psychiatrist.
Finally, as to your being on an antidepressant for the remainder of your life – that is a difficult question, and the answer may depend on how risk-averse you are. The average patient with non-bipolar major depressive disorder will have five to six depressive episodes over a period of 20 years. If a patient has already had two major depressive episodes, the odds are about 70% that he or she will have at least one further episode. For these reasons, most psychiatrists would agree that the average patient with two or more serious episodes of depression should remain on antidepressant medication indefinitely. Perhaps your case is somewhat harder to categorize; on the one hand, your first episode was much milder, but on the other hand, your family history is very strong for major depression.
In general terms, I concur with your psychiatrist’s view, but who knows what the future will bring? We are already investigating the use of magnetic fields to treat depression. Cognitive behavioral therapy is proving to be a robust treatment for depression. Rather than thinking in terms of the remainder of your life, it might be more helpful to reassess the situation every two to three years – but in the mean time, the medication makes a good deal of sense. Good luck with the side effect issue – it is a puzzler!