Treatment of depression has improved enormously over the last four decades. It's a tough treatment and research problem because depression isn't just one diseas

Treatment of depression has improved enormously over the last four decades. It's a tough treatment and research problem because depression isn't just one disease at the biological level. Quoting the full study abstract will probably be helpful to the discussion here. "Background: Ketamine has a rapid antidepressant effect in treatment-resistant depression (TRD). The effects on cognitive function of multiple ketamine infusions and of concurrent antidepressant medication on response rate and duration are not known. Method: Twenty-eight patients with uni- or bipolar TRD were treated over three weeks with either three or six ketamine infusions (0.5 mg/kg over 40 minutes) in the recovery room of a routine ECT clinic. Post-treatment memory assessments were conducted on day 21 (4–7 days after the final infusion). Patients were followed up for six months where possible, with severity of depression and side effects monitored throughout. Results: Eight (29%) patients responded of whom four remitted. Only three (11%) patients had responded within six hours after a single infusion, but in all responders, the response had developed before the third infusion. The duration of response from the final infusion was variable (median 70, range 25–168 days). Discontinuations included two (7%) because of acute adverse reactions during the infusion and five (18%) because of failure to benefit and increasing anxiety. Ketamine was not associated with memory impairment. The ECT clinic was rated suitable by patients and offered appropriate levels of monitoring. Conclusion: This small, open label naturalistic study shows that up to six low dose ketamine infusions can safely be given within an existing NHS clinical structure to patients who continue their antidepressants. The response rate was comparable to that found in RCTs of single doses of ketamine in antidepressant-free patients but took slightly longer to develop." The free full text of the article reporting this preliminary finding can be found online.[1] (Hat tip to the participant here who first found the abstract link, which leads to the full-text link.) Depression is maddeningly difficult to treat because it is quite clear on multiple grounds that not everyone with signs of depression (extremely persistent low mood contrary to the patient's life circumstances) has the same underlying physical or psychological cause of depression. The human mood regulatory system is a SYSTEM, and as such it can be perturbed by a number of biochemical stressors internal to the patient, and also by a number of outside-the-patient environmental stressors (including sleep disturbance, already mentioned in this thread, and the use or abuse of various druggs). Not all patients have the same biological substrate to their depression, so not all patients will respond to the same treatment. To date, the most effective treatment for depression is a both-and of prescribed medication and professionally supervised talk therapy, and there is an active research program on identifying which patients respond to which medicines and to which kinds of talk therapy.[2] In any research program on treatment of human subjects, the studies have to start with small numbers of subjects to verify safety of the treatment, and then gradually increase the number of subjects and add in double-blind protocols to verify both safety and effectiveness. (The study reported here is "open label," not double-blind.) New treatments are usually tested first on patients who don't respond to current treatments, as in the research reported here. It will be a long time before we know how helpful ketamine is compared to other treatments for depression, but that will be an ongoing program of research, and so far it looks somewhat promising. [1] http://jop.sagepub.com/content/early/2014/03/17/0269881114527361.full.pdf+html http://jop.sagepub.com/content/early/2014/03/17/026988111452... [2] http://www.annualreviews.org/doi/abs/10.1146/annurev.psych.121208.131653?prevSearch=depression&searchHistoryKey= http://www.annualreviews.org/doi/abs/10.1146/annurev.psych.1...