Clomipramine has an impressive looking record against other anti-depressants.  It's efficacy is as good as venlafaxine and better than SSRIs.  It has a good safety index, and only slightly more side-effects than venlafaxine.  The use of bethanechol for side-effects should eliminate this side-effect difference.  It is considerably less expensive than venlafaxine ($12 vs. $53-106/month).  Thyroid can give it a further boost if needed. 

Clomipramine was Better than Citalopram or Paroxetine or Moclobemide: Malene Grubbe Hildebrandt, Odense University Hospital in Denmark, Three DB 292 inpatients with major depression. Clomipramine was compared with citalopram, paroxetine, or moclobemide-during 5-week treatment periods. Dropout rates for men and women were similar. Clomipramine therapy produced significantly higher remission rates than any of the others (p = 0.02). Although plasma levels of the drug were significantly higher in female than in male patients, remission rates were nearly the same - about 30%. Hamilton Depression scores did not differ by gender. Further analysis revealed no correlation between plasma drug level, gender, and therapeutic outcome. Am J Psychiatry 2003;160:1643-1650.

Clomipramine Better than Citalopram: 150 MDD 1 week placebo washout. 114 still depressed enough for DB 5 week 150mg/d clomipramine vs 40/g citalopram. Clomipramine 60% complete responders vs 30% for citalopram. Citalopram: clinical effect profile in comparison with clomipramine. A controlled multicenter study. Danish University Antidepressant Group. Psychopharmacology (Berl) 1986;90(1):131-8; One report says two meta-analysis have found clomipramine better than SSRIs for depression though more side-effects.

Clomipramine Better than Desipramine for Body Dysmorphic Disorder: 29 pt DB. 16 weeks crossover study. Even among those patients who are delusional. Clomipramine vs desipramine crossover trial in body dysmorphic disorder: selective efficacy of a serotonin reuptake inhibitor in imagined ugliness. Hollander E, Allen A, Kwon J, Aronowitz B, Schmeidler J, Wong C, Simeon D. Arch Gen Psychiatry 1999 Nov;56(11):1033-9

Clomipramine Better than Fluoxetine; Side-Effects Associated with Positive Response in OCD: 2 multi-center DB industry trials clomipramine v fluoxetine. Response = >35% reduction.58% clomipramine (133/230) and 34% fluoxetine (72/210) responded. Placebo 3% and 8%. Clomipramine side-effects constipation, dry mouth, dizzy each associated with good response. Fluoxetine sex dysfunction associated with 2- to 3-fold increase in response. Comparable in men and women. Initial Fluoxetine nervousness associated with 2-fold increase in response. Nervousness is transient and easily detectable. UCLA, Ackerman, J Clin Psychoph 99;19:459

Isocarboxazide Similar to Clomipramine, Moclobemide in DB: 167 outpatients were allocated to daily treatment with 300 mg moclobemide, 30 mg isocarboxazide or 150 mg clomipramine for 6 weeks. Moclobemide was slightly inferior to clomipramine, whereas isocarboxazide had an intermediate position. There was no interaction between treatment and atypical or nonatypical depression. Anticholinergic symptoms and orthostatic hypotension were most pronounced in the clomipramine group. Larsen, Denmark, Acta Psychiatr Scand 1991 Dec;84(6):564-70

Paroxetine = Clomipramine in Kids: Says 2 DBPC studies shows SSRIs help teen depression but TCAs don’t. DB 8 week 120 MDD teens. Paroxetine 20 or 40/d, Clomipramine 75 or 150/d. Equal efficacy. More side-effects with clomipramine. Paroxetine versus clomipramine in adolescents with severe major depression: a double-blind, randomized, multicenter trial. intent-to-treat analysis, both agents had similar efficacy, with no effect of age; 48.3% and 58.2% of the subjects receiving clomipramine and 65.1% and 59.3% of those receiving paroxetine were rated responders on the MADRS and CGI scales, respectively. Study withdrawals were frequent in both groups (41% and 31%, respectively), but side effects were significantly more frequent with clomipramine (69% versus 49.2%, respectively; p = .027). Braconnier A, Le Coent R, Cohen D; DEROXADO Study Group. J Am Acad Child Adolesc Psychiatry 2003 Jan;42(1):22-9

Clomipramine Better than Paroxetine in Depression: DB 120 MDD in-patients. 12 vs 19 dropouts due to side-effects, but clomipramine more effective. Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. Danish University Antidepressant Group. J Affect Disord 1990 Apr;18(4):289-99

Clomipramine = Sertraline in Depression:166 pt MDD DB. 50-150 mg clomipramine vs 50-200 mg sertraline. Response 71% vs 76% and dropouts from side-effects 17% vs 12%. HAM-D decreased 3% less in clomipramine group. A double-blind study of the efficacy and safety of sertraline and clomipramine in outpatients with severe major depression. Lepine JP, Goger J, Blashko C, Probst C, Moles MF, Kosolowski J, Scharfetter B, Lane RM. Int Clin Psychopharmacol 2000 Sep;15(5):263-71

Clomipramine Better than Venlafaxine in OCD: Random assignment single blind 26 patients venlafaxine 225-350mg/d vs 46 patients on clomipramine. 35% improvement=response. Placebo 6% response vs 36% venlafaxine vs 50% clomipramine. Venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder: a preliminary single-blind, 12-week, controlled study. Albert U, Aguglia E, Maina G, Bogetto F. J Clin Psychiatry 2002 Nov;63(11):1004-9

Venlafaxine & Clomipramine Better in Elderly than Trazodone: DB over 65yo 6wk, venlafaxine 37.5mg bid, clomipramine 25 bid, trazodone 50tid which were increased to 225, 150, and 300/d after 2-3 weeks if needed. 170 pt. S-E lowest with venlafaxine (19%) vs 40% in others. 74% venlafaxine, 69% clomipramine and 57% trazodone pts much improved. Rizzo, Italy, AA 5/30/98

Venlafaxine a Little Better than Clomipramine in Depression: DB 104 pt MDD 8 week. Response Venlafaxine 60% vs 49% clomipramine. 13% venlafaxine side-effect dropouts vs 20% clomipramine. Venlafaxine 60% anti-cholinergic side-effects vs 68% in clomipramine. France. A randomized, double-blind, parallel-group comparison of venlafaxine and clomipramine in outpatients with major depression. Samuelian JC, Hackett D. J Psychopharmacol 1998;12(3):273-8

T3 Thyroid Helps Clomipramine in DB: clomipramine (150 mg/day) associated with a daily dose of 50 micrograms of LT3 (CMI + LT3) compared to a treatment with clomipramine (150 mg/day) (CMI + placebo) for a period of 42 days has been examined in a pilot study, randomized in double-blind conditions, including 20 patients with a normal thyroid status, but presenting a major depressive syndrome (DSM III). The minimum including score was 30 on the Montgomery Asberg Scale (MADRS). The patients were considered as remitted when the MADRS-score was < or = 10. After 28 days of treatment, the efficacy of CMI + LT3 was found to be superior to CMI + placebo (p < 0.05). U Lausanne, Treatment of depression by a combination of clomipramine and triiodothyronine. Souche A, Baumann P, Koeb L, Thermoz P, Azorin JM, Dufour H. Encephale 1991 Jan-Feb;17(1):37-42

More Postural Hypotension in Elderly: Compared side-effects in 150 hospitals MDD pt younger and older than 56. Only difference in 45 side-effects was postural hypotension. Says still can be tolerated up to age 70. Age-related adverse drug reactions to clomipramine. Stage KB, Kragh-Sorensen PB; Danish University Antidepressant Group. Acta Psychiatr Scand 2002 Jan;105(1):55-9