Effexor
Home Up Cymbalta Gepirone Remeron Serzone Reboxetine Effexor

 

Venlafaxine (Effexor)

Venlafaxine has been reported by industry-related psychiatrists to work a little better and a little faster than SSRI anti-depressants, although no better than some of the traditional tricyclics.  However, this claim of venlafaxine being a little better is disputed by an independent review (RN Golden et al, Br J Psychiatry 2002;180:396).  

The standard dose of depression or anxiety is from 75 mg to 225 mg per day with some depressed patients given up to 375 mg per day.  At the present moment, Effexor XR is the most heavily promoted anti-depressant in print, on radio, and on TV with heavy advertising directed at the public.  It is promoted as being a "dual action" anti-depressant, meaning that it increases by serotonin and norepinepherine effects, while SSRIs increase just serotonin.  Venlafaxine's industry-paid psychiatrists promote it as the best anti-depressant available in the world today and strongly urge that it be the first medication a physician prescribes for depression.  However, in fact, venlafaxine is an expensive medicine that has many side-effects and at most minor advantages.  It appears a poor choice as an initial treatment, both due to cost and to side-effects, but a useful third, fourth, or fifth medication to try for patients not responding to nortriptyline, fluoxetine, bupropion, or other more front-line choices.

Venlafaxine comes either as a long-acting Effexor XR taken once a day or the standard Effexor recommended to be taken twice a day.  There is also probably not much advantage to the more expensive XR variety, which will be protected by patent much longer than the already less expensive immediate release form. While the half-life of venlafaxine is quite short at just 5 hours, its metabolite, O-desmethylvenlafaxine, also helps depression and has a half-life of another 11 hours.  One independent research study at the University of Pennsylvania has shown that the standard tablets can also be taken just once a day for a savings of roughly $40 per month at the 75 mg a day dose ($55 vs. $94 wholesale price).  For most patients, 75-100 mg a day will work just as well as higher doses with a considerable cost savings (when using the immediate form).  For patients who are very depressed in the beginning, 150-225 mg per day may relieve the depression more quickly, allowing the lower dose for maintenance.   Unless the medicine is causing insomnia, taking it as a single dose at bedtime will probably allow patients to sleep off some of the side-effects without noticing them.

Venlafaxine side-effects are fairly common.  In initial trials, 19% of 3,000 patients were unable to tolerate the side-effects. That's a high rate.  The most common side-effects to venlafaxine are nausea (26% more common than placebo), sexual difficulties (18%), sleepiness (14%), dizziness (12%), dry mouth (11%), sweating (9%), anorexia (9%), constipation (8%), insomnia (8%), and nervousness (7%). Cholesterol is increased an average of 9 mg/dL.  Venlafaxine can cause a sustained increase in diastolic blood pressure, primarily at the higher doses. Heart rate is increased an average of four beats per minute.

Withdrawal is somewhat more of a problem with venlafaxine due to its shorter half-life. Some psychiatrists have reported difficulties with withdrawal effects from missing a single dose.  Therefore, if taking venlafaxine for more than a week, the medicine should be slowly tapered. For those on the medicine for at least eight weeks, the taper should ideally be from two weeks up to a couple months for long-term users.  There have also been seizure reported in overdose cases (IM Whyte el at, QJM 2002;96:369).  Venlafaxine has a higher fatality rate in overdoses (NA Buckley et al, BMJ 2002;325:1332).  High doses of venlafaxine may produce an amphetamine-like high and abuse has been reported (SP Sattar et al. N Engl J Med 2003;348:764).

Thase Says Venlafaxine Better: Although it has been conventional to assume that all antidepressants are equally effective, evidence from a recent pooled analysis of data from eight double-blind, randomized, controlled clinical studies suggests that venlafaxine therapy may be associated with higher remission rates. U Pitt, Optimizing treatment outcomes for patients with depression and generalized anxiety disorder. Thase ME, Trivedi M. Psychopharmacol Bull 2002 Summer;36 Suppl 2:93-102. Thase says the same is true for tricyclic anti-depressants (TCAs), but claims side-effects are worse with TCAs.  However, bethanechol relieves some of the worst TCA side-effects, but Thase and other industry psychiatrists would not allow its use in comparison trials. "In hospitalized patients, TCAs affecting both serotonergic and noradrenergic systems (eg, amitriptyline or clomipramine) have been found to have greater efficacy when compared with SSRIs." New goals in the treatment of depression: moving toward recovery. Thase ME, Ninan PT. Psychopharmacol Bull 2002 Summer;36 Suppl 2:24-35

Meta-analysis Says Venlafaxine Better than SSRIs and Equal to TCAs: 44 trials with 63 study arms and 4033 patients with depression. Venlafaxine-XR demonstrated a 73.7% success rate, which was statistically significantly greater than that of the studied SSRIs (61.1%) and TCAs (57.9%) (P<0.001). Comparison of extended-release venlafaxine, selective serotonin reuptake inhibitors, and tricyclic antidepressants in the treatment of depression: a meta-analysis of randomized controlled trials. Einarson TR, Arikian SR, Casciano J, Doyle J, J Clin Ther 1999 Feb;21(2):296-308

Suicides & Attempts No Higher with Placebos vs Citalopram or Venlafaxine XR: DB PC studies with either citolopram or venlafaxine XR. 23,201 pt. 32 suicides, 172 attempts. Rates with placebos 0.5 suicides and 6.7 attempts per year, 0.9 with comparator active meds, and 0.6 and 6.3 attempts per year with citalopram or venlafaxine. Symptoms reduction 47.9% with citalopram or venlafaxine, 47.5% with comparator, and 35.5% with placebo. Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: a replication analysis of the Food and Drug Administration Database. Khan A, Khan SR, Leventhal RM, Brown WA.

Manufacturer Warns Not to Give Venlafaxine to Children: Shortly after GSK warned not to give Paxil to children because of more children and teens attempting suicide on Paxil than on placebo, the venlafaxine manufacturer gave the same warning. (NY Times 2/12/04)

Venlafaxine Better than Placebo: XR 75-225/d 191 MDD pt. Nausea highest first week, 50% less second week and at placebo levels third week. Efficacy and tolerability of once-daily venlafaxine extended release (XR) in outpatients with major depression. The Venlafaxine XR 209 Study Group. Thase ME. J Clin Psychiatry 1997 Sep;58(9):393-8

Venlafaxine Better than SSRIs: Review of DB studies. Achieving remission from depression with venlafaxine and venlafaxine extended release: a literature review of comparative studies with selective serotonin reuptake inhibitors. Rudolph RL. Acta Psychiatr Scand Suppl 2002;(415):24-30

Venlafaxine Better than SSRIs, but Equal to TCAs: Analysis 25 studies vs. SSRIs and 7 vs. TCAs. Kaiser. Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. Smith D, Dempster C, Glanville J, Freemantle N, Anderson I. Br J Psychiatry 2002 May;180:396-404

Venlafaxine Equal to Amitriptyline: DB 118 MDD pt 8 weeks, 150mg/d each med. Equal efficacy. Somewhat more side-effects with amitriptyline. Double-blind comparison of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia. Benedictis E. J Psychopharmacol 2000 Mar;14(1):61-6, Sao Paolo

Venlafazine and Clomipramine Better in Elderly than Trazadone: DB over 65yo 6wk, venlafaxine 37.5mg bid, clomipramine 25 bid, traz 50tid which incr 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% venl, 69% clom and 57% traz pts much improved. Rizzo, Italy, AA 5/30/98

Venlafaxine = > Clomipramine: 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

Venlafaxine = Desipramine = Sertraline for Low & High Angry Patients: 158 MDD pt in six cell study. Efficacy similar in every cell. Differential pharmacological treatment response in high angry hostile and low angry hostile depressed patients: a retrospective analysis. Not clear is random assignment or any blindedness. Bagby RM, Kennedy SH, Schuller DR, Dickens SE, Minifie CE, Levitt A, Joffe R. J Affect Disord 1997 Sep;45(3):161-6

Venlafaxine = Dothiepin for Elderly: 92 >65yos MDD. No difference in efficacy. Dropout 7% venlafaxine vs 8% dothiepin. A randomised, double-blind, parallel-group comparison of venlafaxine and dothiepin in geriatric patients with major depression. Mahapatra SN, Hackett D. Int J Clin Pract 1997 Jun;51(4):209-13

Venlafaxine = Fluoperazine: 104 pt 6 week DB Response 70% vs 66%. Increased remission rates with venlafaxine compared with fluoxetine in hospitalized patients with major depression and melancholia. Remission 41% vs 36%. Greece, Tzanakaki M, Guazzelli M, Nimatoudis I, Zissis NP, Smeraldi E, Rizzo F. Int Clin Psychopharmacol 2000 Jan;15(1):29-34

Venlafaxine = Fluoxetine: 359 pt 12 week DB MDD + anxiety. 10% vanlafaxine side-effect dropout vs 7 % fluoxetine. 67% vs 72% vs 43% response rate. Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. Venlafaxine XR 360 Study Group. Alberta: Silverstone PH, Ravindran A. J Clin Psychiatry 1999 Jan;60(1):22-8

Venlafaxine = Fluoxetine: 382 pt 8 wk DB MDD. Similar results and rate of side-effects. Randomized, double-blind comparison of venlafaxine and fluoxetine in outpatients with major depression. Costa e Silva J. J Clin Psychiatry 1998 Jul;59(7):352-7

Venlafaxine XR > Fluoperazine or Placebo: 8 wk study DB PC 301 pt V-XR 75mg/d, flu 20mg/d with increases possible to 225mg and 60mg. 71% V-XR vs 62% flu vs 52% placebo much improved. Aguiar, Wyeth, APA 5/30/98 Toronto

Venlafaxine XR > Fluoxetine: A Venlafaxine drug industry sponsored study found Venlafaxine XR more quickly effective in treating depression than fluoxetine 20-60 mgQD which significant remission of depression over placebo already noted in a significant number of patients by week 3. However, the real differences between the meds were quite small although venlafaxine 75-225 QD appeared to be somewhat better at helping anxiety in addition to depression. Silverstone, U Alberta, J Clin Psychiatry 1/99 60:22-8

Venlafaxine > Fluoxetine: DB 146 x 12 weeks of moderately depressed rx venlafaxine 75-150 vs fluoxetine 20-40/d. 59% vs 40% remission. Dosage increase permitted after 2 weeks and done in 37% of venlafaxine pts. vs 53% fluoxetine. Side-effects similar. Venlafaxine compared with fluoxetine in outpatients with depression and concomitant anxiety. De Nayer A, Geerts S, Ruelens L, Schittecatte M, De Bleeker E, Van Eeckhoutte I, Evrard JL, Linkowski P, Fossion P, Leyman S, Mignon A. Int J Neuropsychopharmacol 2002 Jun;5(2):115-20

Venlafaxine > Fluoxetine for MMD with GAD: DB PC 368 MDD of whom 92 also GAD. Response, defined as > or = 50% decrease in symptoms score, was achieved in 66% and 59% of the comorbid patients for HAM-D and HAM-A, respectively, in the venlafaxine XR group at week 12. This response was higher than that seen with fluoxetine (52% and 45%) or placebo (36% and 24%). Comorbad patients slower to respond. Efficacy of venlafaxine extended release in patients with major depressive disorder and comorbid generalized anxiety disorder. U Alberta, Silverstone PH, Salinas E., J Clin Psychiatry 2001 Jul;62(7):523-9

Venlafaxine > Fluoxetine Due to Anxiety Factor: Analysis 6 BD with 542 venlafaxine and 555 fluoxetine patients found venlafaxine’s advantage may be attributed to its advantage on anxiety. Duke, Achieving remission with venlafaxine and fluoxetine in major depression: its relationship to anxiety symptoms. Davidson JR, Meoni P, Haudiquet V, Cantillon M, Hackett D. Depress Anxiety 2002;16(1):4-13

Fluvoxamine = Venlafaxine for In-patient Psychotic Depression: No difference were found in this DB PC study that was not financed by the venlafaxine manufacturer.  R Zanardi et al, J Clin Psychiatry 2000;61:26). 

Sertraline = > Venlafaxine for Elderly Depressed: Small 53 pt 82yo average 10 week study DB PC. Meds to 100mg sertraline and 150mg venlafaxine. 83% had heart disease. Both similar in speed and efficacy, but venlafaxine more serious side-effects and increased heart rate. Probing the Safety of Medications in the Frail Elderly: Evidence From a Randomized Clinical Trial of Sertraline and Venlafaxine in Depressed Nursing Home Residents. Oslin DW, Ten Have TR, Streim JE, et al. Journal of Clinical Psychiatry. 2003;64(8):875-882

Fluoxetine < Nortriptyline and Venlafaxine for Melancholia: Two studies have found this. A third retrospective study reports that of nine patients to develop melancholia while already on anti-depressant, all were on an SSRI. They responded quickly to non-SSRI meds. Guadagno, East Tenn State U, APA 5/30/98 Toronto

Venlafaxine > Imipramine on Life Functioning : Two DB PC studies by the manufacturers of Effexor with 459 depressed patients for "up to" 6 weeks report their medication worked better on a general life functioning scale developed by NIMH. Can improvement in well-being and functioning be distinguished from depression improvement in antidepressant clinical trials? Pedersen RD, Pallay AG, Rudolph RL. Qual Life Res 2002 Feb;11(1):9-17

Venlafaxine = > Imipramine Maintenance: DB 1 year study 290 pt on venlafaxine, 91 imipramine, both 75-225 mg/d. Trend in favor of venlafaxine. Eastside, New York City. Long-term safety and clinical acceptability of venlafaxine and imipramine in outpatients with major depression. Fewer side-effects said important in favor of venlafaxine. Shrivastava RK, Cohn C, Crowder J, Davidson J, Dunner D, Feighner J, Kiev A, Patrick R. J Clin Psychopharmacol 1994 Oct;14(5):322-9

Venlafaxine = > Imipramine at Penn: 244 pt DB PC 6 week aver max 182mg venlafaxine 176mg/d imipramine. 90% and 79% improved. Side-effect dropout 15% vs 24%. Comparison of venlafaxine and imipramine in the acute treatment of major depression in outpatients. Schweizer E, Feighner J, Mandos LA, Rickels K. J Clin Psychiatry 1994 Mar;55(3):104-8

Venlafaxine > Imipramine: 229 pt DB PC Parisian study. Efficacy of venlafaxine in depressive illness in general practice. Lecrubier Y, Bourin M, Moon CA, Schifano F, Blanchard C, Danjou P, Hackett D. Acta Psychiatr Scand 1997 Jun;95(6):485-93

Venlafaxine Faster Than Imipramine in Helping Depressed Melancholia: DB MDD melancholic inpatients rx venlafaxine 375/d vs imipramine 200/d. Response rate in both equal but time to average response 14 days venlafaxine vs. 21 days imipramine. More side-effects imipramine. A randomized, double-blind comparison of a rapidly escalating dose of venlafaxine and imipramine in inpatients with major depression and melancholia. U Mainz: Benkert O, Grunder G, Wetzel H, Hackett D. J Psychiatr Res 1996 Nov-Dec;30(6):441-51

Venlafaxine = Mirtazapine in MDD: 157 pt DB in-patient severe MDD 8 wk. 15% venlafaxine vs 5% mirtazapine dropout due to side-effects. 63% mirtazapine vs 55% venlafaxine (75-375/d). Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features. France: Guelfi JD, Ansseau M, Timmerman L, Korsgaard S; Mirtazapine-Venlafaxine Study Group. J Clin Psychopharmacol 2001 Aug;21(4):425-31

Paroxetine=Venlafaxine for BAD Depr, Venlafaxine More Mania: 55 pt blind investigator random assign 6 wk study aver 30mg paroxetine or 180 venlafaxine. 43% & 48% responded with 33% both groups remitting. 3% v 13% became manic or hypomanic despite mood stabilizer. J Clin Psych 02;63:508.

Venlafaxine > Sertraline: 148 pt MDD out-patients DB. 75 bid vs 50 bid. Not XR. U Tampere. Remission (HAM-D <10) 67% vs 36%. Response 81% vs 67%. Side-effects dropouts similar. Randomized, double-blind comparison of venlafaxine and sertraline in outpatients with major depressive disorder. Venlafaxine 631 Study Group. Mehtonen OP, Sogaard J, Roponen P, Behnke K. J Clin Psychiatry 2000 Feb;61(2):95-100

Venlafaxine = Trazodone: DB PC 6 wk 225 pt. Abstract unclear but both better than placebo and probably equal efficacy. 60% finish the 6 week study. 91 stayed in DB for one year with venlafaxine patients more likely to stay in study 1 yr. Vine Street Clinic. A comparison of venlafaxine, trazodone, and placebo in major depression. Cunningham LA, Borison RL, Carman JS, Chouinard G, Crowder JE, Diamond BI, Fischer DE, Hearst E. J Clin Psychopharmacol 1994 Apr;14(2):99-106

No Mania in Bipolar Study: U Penn study by Amsterdam with QD vs BID venlafaxine groups for bipolar II vs unipolar found no diff and no mania within 6 wk of study. J Clin Psychopharm 10/98

Low Dose Venlafaxine No Help in Child-Teen Study: DB PC 33 MDD 8-17yos 6 week with no benefit. Venlafaxine in the treatment of children and adolescents with major depression. Mandoki MW, Tapia MR, Tapia MA, Sumner GS, Parker JL. Psychopharmacol Bull 1997;33(1):149-54

DB Better than Placebo, 75mg Best for Most: Industry-funded multicenter study with only 194 of 358 pt completion study of placebo or 75 mg, or 225 or 375/d. Dropouts 59% placebo, 56% 75mg, and 51% for each higher dose group. 225 and 375 modestly better but 75 mg group had fewer S-E with Side-effect dropouts = 5% placebo, 17%, 24%, and 30% respectively. Wyeth Labs: A randomized, placebo-controlled, dose-response trial of venlafaxine hydrochloride in the treatment of major depression. Rudolph RL, Fabre LF, Feighner JP, Rickels K, Entsuah R, Derivan AT., J Clin Psychiatry 59:116-22, ’98

150mg or 200mg Faster than 75mg: 384 MDD pt DB PC with improvement in 1-2 weeks noted especially in higher dose groups. Dose related responsiveness still noted at 12 weeks. Abstract has little data. ( Authors claim well tolerated as do all published studies, but industry summary of studies show above average dropout rate and considerable number and rate of side-effects. An issue of publication bias where the more favorable studies are more likely to get published?) U Wash. The use of venlafaxine in the treatment of major depression and major depression associated with anxiety: a dose-response study. Venlafaxine Investigator Study Group. Khan A, Upton GV, Rudolph RL, Entsuah R, Leventer SM. J Clin Psychopharmacol 1998 Feb;18(1):19-25

375mg Faster than 225 or 75: 60 pt 1st DB study. All apparently helped. U Penn. Placebo-controlled trial of venlafaxine for the treatment of major depression. Schweizer E, Weise C, Clary C, Fox I, Rickels K. J Clin Psychopharmacol 1991 Aug;11(4):233-6; Same Phase II study. 93 more patients. No report of differential effectiveness in abstract. Venlafaxine in depressed outpatients. Khan A, Fabre LF, Rudolph R. Psychopharmacol Bull 1991;27(2):141-4

Venlafaxine 75mg = 150 > Buspirone for GAD: DB PC 401 pt 8 weeks. Buspirone 10 tid. Not much difference in side-effects supposedly. Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. Duke: Davidson JR, DuPont RL, Hedges D, Haskins JT. J Clin Psychiatry 1999 Aug;60(8):528-35

75mg = 150mg > 37.5mg for GAD: 541 pt DB PC 24 weeks. XR. No difference in dropout rates. Venlafaxine extended release (ER) in the treatment of generalised anxiety disorder: twenty-four-week placebo-controlled dose-ranging study. Allgulander C, Hackett D, Salinas E. Br J Psychiatry 2001 Jul;179:15-22

Lowest Dropouts on 150mg vs Lower: Two DB studies of GAD 6 months 37.5 vs 75 vs 150mg XR QD. Effectiveness of venlafaxine, extended release formulation, in the short-term and long-term treatment of generalized anxiety disorder: results of a survival analysis. Montgomery SA, Mahe V, Haudiquet V, Hackett D. J Clin Psychopharmacol 2002 Dec;22(6):561-7

High Dose 450-600 Called Safe: 5 rx-resistant MDD rx high dose. 4 responded. Safety and efficacy of high dose of venlafaxine XL in treatment resistant major depression. Mbaya P. Hum Psychopharmacol 2002 Oct;17(7):335-9

Venlafaxine QD Dosing Fine: DB study 48 MDD pt Rx bid vs qd x 6 weeks. Started 37.5/day and increased to 225/day. No significant differences tho trend for more rapid improvement with bid dosing. (Ed: probably coincidental only). No difference in side-effects. U Penn. Once- versus twice-daily venlafaxine therapy in major depression: a randomized, double-blind study. Amsterdam JD, Hooper MB, Amchin J. J Clin Psychiatry 1998 May;59(5):236-40

Wyeth Study Reporting XR Better: DB study MDD. No mention in article of # of patients or duration or efficacy or dropouts. Says Benefit/Risk ratio for nausea and dizziness favors XR by 2:1. A benefit-risk analysis of once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Entsuah R, Chitra R. Psychopharmacol Bull 1997;33(4):671-6. It is worth noting that Wyeth has a lot of money riding on this finding. It could be a bad case a massaging the data.

Vine Street Clinic Finds XR Better: DB PC 278 pt MDD 12 weeks. 75-150mg/d. Both better than placebo at same stages but at 12 weeks XR better than IR. Once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Venlafaxine XR 208 Study Group. Cunningham LA. Ann Clin Psychiatry 1997 Sep;9(3):157-64. Study undoubtedly handsomely funded by Wyeth.

Withdrawal Reactions a Problem: SSRIs are clearly associated with a higher risk of withdrawal syndrome (OR: 5.05) and in particular with venlafaxine and paroxetine (OR: 12.16 and OR: 8.47, respectively). The risk of withdrawal reactions appears to be greater with short half-life drugs such as paroxetine and venlafaxine. Reports of withdrawal syndrome with the use of SSRIs: a case/non-case study in the French Pharmacovigilance database. Trenque T, Piednoir D, Frances C, Millart H, Germain ML. Pharmacoepidemiol Drug Saf 2002 Jun;11(4):281-3; Half-life 5 hr with half-life of active metabolite O-desmethylvenlafaxine 11 hr. T-max of venlafaxine 2 hr and O-desmethyl 3 hr. With XR, these are 5 hr and 9 hr.

Venlafaxine Withdrawal Symptoms Common: After 8 week DB trial of XR, nine were switched abruptly to placebo and nine continued. 7 of 9 with venlafaxine stopped had average of 3 side-effects vs only 2 of 9 continuing on venlafaxine reporting side-effects. Fava M et al: Emergence of adverse events following discontinuation of threatment with extended-release venlafaxine. Amer J Psyc 97;154:1760-2. MGH/Wyeth

Causes SIADH: Four cases in elderly reported. All full recovery in average of 9 days. Holoham, Penn State, APA 5/30/98 Toronto

Benztropine for venlafaxine-induced night sweats. Letter. Pierre JM, Guze BH. J Clin Psychopharmacol 2000 Apr;20(2):269

Benztropine in the treatment of venlafaxine-induced sweating: Garber A, Gregory RJ. J Clin Psychiatry 1997 Apr;58(4):176-7

Breast Enlargement in 39% From SSRIs, Venlafaxine: 59 women in study on meds >2months. Of women getting this side-effect, 84% had gained weight. Prolactin levels were increased in paroxetine group only. Breast enlargement during chronic antidepressant therapy. Amsterdam JD, Garcia-Espana F, Goodman D, Hooper M, Hornig-Rohan M. J Affect Disord 1997 Nov;46(2):151-6

An SSRI at Low Dose, Noradrenergic at Higher: Study with healthy adults. Both 75mg venlafaxine and sertraline inhib platelet 5-HT while maprotiline did not. Both 375mg/d venlafaxine and meprotiline blunted pressor response to tyramine, whereas sertraline and low venlafax did not. Venlafaxine low dose side-effect = nausea, vomiting, GI and sex diff similar to an SSRI. High dose venlafaxine also had sweating, dry mouth, increased heart rate, and BP, similar to NE uptake inhibitors. Harvey AGP 00;57:503

Blood Level Correlated with Efficacy: 89 patients tested for dose vs blood level and 22 tested with serial MADRS and blood level. A moderate correlation between daily doses and plasma concentrations, together with a higher relationship between improvement on the MADRS scale and concentration. Moreover, plasma concentrations (for venlafaxine and its predominant metabolite, O-desmethylvenlafaxine) up to 400 microg/l can be considered as effective. U Liege. Venlafaxine: the relationship between dose, plasma concentration and clinical response in depressive patients. Charlier C, Pinto E, Ansseau M, Plomteux G. J Psychopharmacol 2002 Dec;16(4):369-72

Hyponatremia Very Common: Elderly patients on SSRIs or venlafaxine were 5.6 times as likely as patients not so treated to have hyponatraemia. Thirty-nine percent of patients on an SSRI or venlafaxine had hyponatraemia compared with 10% of controls. Ten of the 14 patients on venlafaxine were hyponatraemic. Hyponatraemia in elderly psychiatric patients treated with Selective Serotonin Reuptake Inhibitors and venlafaxine: a retrospective controlled study in an inpatient unit. Kirby D, Harrigan S, Ames D. Int J Geriatr Psychiatry 2002 Mar;17(3):231-7