GETTING THE BEST OUT OF ANTIDEPRESSANTS

Can lithium help the tricyclic-refractory depressive? Depressives unresponsive to tricyclic antidepressants usually face one of several options: an escalation of dose, which may increase side errects without compensating benefit; an often useless switching from one drug to another; mult iple prescriptions including other tricyclics , tet racycJic:s, MAO-inhibitors. or even methylphenidate or tri-iodolhyronine: IV therapy; or ECT. Only ECf produces rapid amelioration of severe symptoms, but it has sociaJ, legal and other drawbacks. For most refractory patients the outlook is bleak . They face prolonged depression , and al l that goes with iI, including the risk of suicide. But perhaps no longer. Animal research has show n that tricyclics increase the sensitivity of neurons to serotonin. Lithium, it seems. enhances the efficiency of the serotonin system. So perhaps lithium could sensitise the serotonin receptors and make them more responsive to the tricyclic:s. A preliminary cl inical study of 17 patients appears to have confi rmed this hypothesis, for lithium carbonate 300mg tid, added to the patient's regular tricyclic, produced marked al leviat ion of symptoms in [1-24 hours, in both psychotic and non-psychotic depression, an effect which persisted for 3·9 months' follo ..... ·up. DiSCOnlinuation of lithium resulted in a partial return of symptoms in 2, which was reversed in 1 by reintroducing lith ium . The therapeutic effect could not be attributed to a pharmacokinetic interaction , and the treatment was well tolerated except for I patient with abdom inal pain. If lithium is as safe and efficac.oous as it seems, then no other therapeutic option offers such hope of rapid and substantial relief,

and s ince it is so rapid, the physician should know quickly if it is going to work. tnternational Dn18 Therapy Newsleuer 16: 2S (ScI' 19& 1)

Now, how does one approach maintenance in the major depressive disorders? There are 2 types of maintenance therapy: 'continuation' therapy and 'long-term prevenlive' therapy, the former approach being based on the assumption that the drug suppresses symptoms without affecting the underlying disorder. There are 2 critical questions concerning oontinuation therapy: once symptoms have subsided, is it necessary? And ifso, at what dose and for how long? The first question seems answered by the fact that relapse rates when the drugs are discontinued (or replaced by placebo) may average over 50%, oompared with 22 % when the drug is continued. Ideally, then, treatment should continue until the depressive episode spontaneously stops, and there may be markers (for example, the dexamethasone suppress ion lest) which might

soon tell us when that happens. Continuation therapy might be approached in several ways. Some clinicians maintain the full dose for several months, some cut

back to a half·dose or less; others rapidly reduce dose; and others reduce it slowly. International Dr\l& T1Ierapy Newsletter 16: 27 (ScI' t981)

12 INPHARMA 19Sep \98\ 0156_2703 / 81 / 0919_0012 $OO.SO / O C ADIS Press