Acupuncture No Clear Benefit for Depression: In a meta-analysis of random assignment controlled studies of either manual acupuncture or electroacupuncture compared with any control procedure in subjects with depression, 7 randomised comparative trials involving 509 patients were included. The evidence is inconsistent on whether manual acupuncture is superior to sham, and suggests that acupuncture was not superior to waiting list. Evidence suggests that the effect of electroacupuncture may not be significantly different from antidepressant medication, weighted mean difference -0.43(95% CI -5.61 to 4.76). There is inconclusive evidence on whether acupuncture has an additive effect when given as an adjunct to antidepressant drugs. The effectiveness of acupuncture for depression--a systematic review of randomised controlled trials. Mukaino Y, et al. Peninsula Medical School, Exeter, UK. . Acupunct Med. 2005 Jun;23(2):70-6.

Acupuncture Very Small Study Reports Possible Benefit: In a DB PC study of 30 depressed patients receiving either active or inactive laser acupuncture treatment twice weekly for 4 weeks and then weekly for 4 more weeks, Beck Depression Inventory scores fell from baseline by 16.1 points in the intervention group and by 6.8 points in the sham control group (P<0.001). Laser acupuncture for mild to moderate depression in a primary care setting--a randomised controlled trial. Quah-Smith JI, et al. Monash University, Victoria, Australia. . Acupunct Med. 2005 Sep;23(3):103-11. Ed: Acupuncture has a very poor track record in studies for other diseases.  This is probably a fluke finding due to the very small size and other factors.

Mefipristone, a Glucocorticoid Receptor Antagonist, for Psychotic Depression: Five patients with psychotic major depression given 600 mg of mifepristone in a 4-day, double-blind, placebo-controlled crossover study. Adverse effects were not observed. All showed substantial improvements on Hamilton and BPRS. Little, if any, improvement with placebo. Suggest that short-term use of GR antagonists may be effective in the treatment of psychotic major depression. J Clin Psychopharmacol 2001 Oct;21(5):516-21

Mecamylamine Helped Depressed Tourette's Children: In a small DB PC study of 50 children with Tourette's and at least one mood disorder, an old anti-hypertensive helped those with depression, rage, and irritability although the numbers were quite small. P Sanberg, USF, Molecular Psychiatry 5/06. USF holds the patent.

Nimodipine/Carbamazepine for Affective: DB PC of nimodipine (Nimotop, calcium channel blocker)in 30 refractory affective illness. 10 responded. 14 non-responders had carbamazepine added with four responders. Less than ideal study design. Pazzaglia, NIMH, J Clin Psychopharm 98;18:404

Pramipexole dopamine D2/D3 agonist Supposedly Helped as Adjunct: 6 pt in open trial of adding to anti-depressant showed benefit, often rapidly. Well tolerated. Steve Kendell, Long Beach VA, APA 5/99. Also Am J Psychiatry 5/99; 156:798 Two cases refractory bipolar I depression. Pramipexole (Mirapex) used for Parkinson’s disease.

Pramipexole Supposedly Helped as Adjunct: Pramipexole for refractory MDD was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses, 19 completed the 16-week follow-up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 ± 8.4 at baseline to 13.9. U Pisa, U Pitt. Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB. Pramipexole in treatment-resistant depression: a 16-week naturalistic study. Bipolar Disord 2002: 4: 307-314 (Ed: These open trials aren't worth very much although the decrease in depression scores was impressive.)

Tianeptine Serotonin Reuptake Agonist Helps: Tianeptine, which enhances serotonin reuptake, is an effective antidepressant. Waintraub L, Septien L, Azoulay P. Efficacy and safety of tianeptine in major depression: Evidence from a 3-month controlled clinical trial versus paroxetine. CNS Drugs. 2002;16:65-75.

Tolcapone May Help Depression: It’s a catechol-O-methyltransferase (COMT) inhibitor that has shown efficacy in the treatment of Parkinson's disease. Assess the effects of tolcapone on the choline and myoinositol resonances in the left caudate and dorsolateral frontal lobe through proton magnetic resonance spectroscopy and on whole blood levels of S-adenosyl-L-methionine (SAMe). 21 adults with MDD, initial score of > or = 16 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17). openly for 8 weeks with tolcapone 400 mg twice daily. Among all subjects (N = 21), there were significant (p < .0001) decreases at endpoint in HAM-D-17 scores (from 19.4 2.9 to 10.7 5.5), CGI-S scores (from 3.9 0.6 to 2.4 1.1), and BDI scores (from 21.6 8.1 to 12.3 8.6). Eight patients (38%) dropped out because of diarrhea, elevated liver function tests, increased anxiety, and noncompliance. No significant effects were noted on choline and myoinositol resonance or on SAMe levels Mass Gen. J Clin Psychopharmacol 1999 Aug;19(4):329-35. Tolcapone or entacapone in Parkinson’s disease inhibits COMT degradation of levodopa and prolongs its action altho dopamine agonists may be better. The COMT inhibitors increase on-time and decr off-time. Dopaminergic tremors from tolcapone require downward adjstment of levodopa if they occur. Tolcapone can cause explove diarrhea or liver dysfunction.

Yohimbine As Adjunct for SSRI and ECT: Presynaptic alpha2-adrenergic autoreceptors inhibit release of NE into the synapse. A similar alpha2-adrenerigc receptor, a heteroreceptor on the presynaptic terminal of serotonergic neurons, when stimulated by NE I, inhibts release of serotonin. Reports suggest yohimbine, an alpha2-adrenoceptor antogonist, potentiates the anti-depressant effects of serotonergic drugs (fluvoxamine) and ECT. Biol Psychiatry 38:765-67, ’95. J Clin Pscyhiatry 47:508-10