Citalopram (Celexa) and Escitalopram (Lexapro)

Citalopram is another useful SSRI but with no evidence that it works any better than any other except paroxetine (Paxil), although there may be some patients in whom it works best.  It has the advantage, like sertraline (Zoloft), of not interfering with other medications as much as fluoxetine and paroxetine do.  The manufacturer has recently come out with a refined single left isomer escitalopram (Lexapro), which is exactly the same as citalopram without the inactive right isomer.  Lexapro appears to be of no advantage over the standard citalopram, although the manufacturer now claims it is much better.  Of course, a few years ago, when Celexa was still covered by patent, Celexa was manna from heaven. There is little doubt that the manufacturer came out with the new product in order to extend its profits by getting a new patent on just the left-handed isomer.  This strategy is already working despite no good evidence that escitalopram is any better.  In fact, I have had a couple patients, who have tried both, tell me the original citalopram works better for them.

Citalopram has been shown in extensive research to work as well as many other anti-depressants but not really any better than most.  Like all SSRI medications, it has far fewer anti-cholinergic side-effects than the older tricyclics, although it has its own side-effects.  Like other SSRIs, it does not cause weight gain, although sexual complaints are very common. The preferred dose for the  majority of people is 20 mg per day in a single dose, probably best taken in the morning.

Citalopram is slightly more expensive than fluoxetine, but still a very good deal.  It works no better on average, for the vast majority of patients being put on an SSRI, but the lack of drug interactions make it very attractive.  Because of this, it is my favorite SSRI and one of my front-line treatments for depression.  Also, some patients will respond to one SSRI but not another.  Thus, trying citalopram for those not responding to fluoxetine, nortriptyline, trazodone, or bupropion might be very worthwhile. 

Citalopram does have an advantage over fluoxetine for patients on certain medications metabolized by liver enzymes that fluoxetine blocks.  

Citalopram is the newest of the SSRIs. It appears as good as the other SSRIs with similar strengths and weaknesses. Like other SSRIs, it has a high safety index, causes little or no weight gain, is a good choice for the elderly, works for OCD, but has a high rate of sexual side-effects. The manufacturer recommends starting at 20 mg/day then increasing it to 40 mg/day with some patients taking up to 60 mg/day. Escitalopram separates out the active left-handed isomer of citalopram, meaning that only half the level of medication is required to achieve the same effect. The promotional material for escitalopram claims that it causes fewer side-effects. However, the research evidence of this is far from clear as noted below. The half-life of either is 35 hours, so once a day dosing is fine. The elderly should take only 20 mg/day of citalopram or 10 mg of excitalopram because of slower clearance in the elderly.

Of 1063 patients in clinical trials, 16% discontinued citalopram due to side-effects, especially for nausea, insomnia, dizziness, and drowsiness. Side-effects in percentages reported more often than for placebo were: drowsiness (8%), nausea (7%), dry mouth (6%), ejaculatory difficulty (5%). Side-effects in the 2%-3% range were: sweating, tremor, diarrhea, fatigue, sinusitis, rhinitis, and impotence. Other research, using a different method for gathering patient reports of sexual side-effects, finds up to 70% of patients notice some level of difficulty.

Of 1312 patients in the escitalopram trials, only 6% discontinued because of side-effects. However, the escitalopram results are highly questionable. For unknown reasons, only 2% of placebo patients discontinued in the escitalopram trials vs. 8% in the citalopram trials. The same is true of the reports of individual placebo side-effects in the two sets of trials. For instance, in the citalopram trials, 14% of placebo patients reported dry mouth. In the escitalopram trials, only 5% made such a report. This suggests that the escitalopram trials were much less likely to elicit reports of side-effects that the citalopram trials.

Side-effects were also twice as high on the 20 mg/day dose of escitalopram as on the 10 mg/day. The 20 mg/day dose had a 10% discontinuation rate. However, the 10 mg/day treatment level was much more common in the escitalopram studies, meaning that the amount of active medicine received by the average patient in the escitalopram trials were considerably lower than in the citalopram trials. In the citalopram clinical trials, the dosage ranged from 10 mg/day up to 80 mg/day with side-effects increasing as the dose increased. In summation, it is not at all clear that escitalopram really has fewer side-effects than citalopram and the difference is certainly much less than a superficial reading of the manufacturer listing in the PDR would at first lead you to believe. There appears to be little reason to take escitalopram, which was developed by the manufacturer for the sole purpose of extending its patent protection since citalopram is now available in a much less expensive generic.

Citalopram:  It has a low p450 inhibition. Nausea 21% v 14%, somnolence 18% v 10%, Diarrhea 8% v 5%, ejaculatory difficulty 6% v 1%. SSRI. Half-life 35 hr. Cimetidine increases citalopram levels. Citalopram increases imipramine levels. It is as effective as fluoxetine and sertraline and better than placebo. 12 fatalities have occurred with citalopram ODs. More sexual dysfunction than sertraline. Nausea, dry mouth, somnolence, delayed ejaculation. Start at 20 mg/d and may increase weekly. Med Letter 12/4/98 says no advantages. Wholesale price: $6/mo vs. fluoxetine $3, Paxil XR $67, sertraline (Zoloft) $68.

Citalopram Maintenance Better than Placebo But ? Abrupt D/C: In a DB PC study of 120 patient with major depression, those responding to citalopram within 8 weeks were randomized at 24 weeks to either citalopram or placebo for an additional 48 weeks. The abstract doesn’t mention if those put on placebo were weaned off citalopram or stopped abruptly. Efficacy of citalopram in the prevention of recurrent depression in elderly patients: placebo-controlled study of maintenance therapy. Klysner R, Bent-Hansen J, et al. Denmark. Br J Psychiatry 2002 Jul;181:29-35

Citalopram Maintenance Helps at 20, 40, or 60 mg/d: In a Swiss study of patients responding to citalopram in 6-9 week open treatment then placed in a DB PC study for 48-77 weeks. All citalopram groups did well. The abstract doesn’t clarify if the discontinuation was abrupt in the placebo group. Prophylactic effect of citalopram in unipolar, recurrent depression: placebo-controlled study of maintenance therapy. Hochstrasser B, Isaksen PM, et al.

Citalopram Maintenance at 20 Fine, Placebo Responders Likely to Relapse: 147 pt responding in the DB PC 6 week trial of citalopram put in maintenance DB PC for 24 weeks. No difference between 20 or 40mg/d in preventing relapse. Relapse rate for placebo responders same as relapse rate for those responding to citalopram in 6 weeks study then randomized to placebo. A 24-week study of 20 mg citalopram, 40 mg citalopram, and placebo in the prevention of relapse of major depression. St. Mary’s-London: Montgomery SA, Rasmussen JG, Tanghoj P. Int Clin Psychopharmacol 1993 Fall;8(3):181-8

Citalopram 20, 40, 60/d All Help OCD: DB PC 401 pt. Response defined as 25% improvement on Y-BOCS. 57%, 52%, and 65% responders vs. 37% with placebo. Citalopram 20 mg, 40 mg and 60 mg are all effective and well tolerated compared with placebo in obsessive-compulsive disorder. Montgomery SA, Kasper S, Stein DJ, Bang Hedegaard K, Lemming OM. Imperial College of Science-London: Int Clin Psychopharmacol 2001 Mar;16(2):75-86

Citalopram 20-30/d > 10-15 or 40-60 > Placebo for Phobic Panic: DB PC 475 pt 8 weeks also included clompiramine. 279 continued in maintenance. All doses of citalopram better than placebo, but 20-30/d best. Clompramine less consistent. Patients improved further on maintenance. Citalopram controls phobic symptoms in patients with panic disorder: randomized controlled trial. Leinonen E, Lepola U, Koponen H, Turtonen J, Wade A, Lehto H. J Psychiatry Neurosci 2000 Jan;25(1):25-32

Citalopram and Escitalopram Help Panic: A manufacturer's DB PC study of 366 panic disorder patients with or without agoraphobia found that both meds did better than placebo. Discontinuation rates were similar to placebo in the 6-8% range. Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial. Stahl SM, Gergel I, Li D. J Clin Psychiatry. 2003 Nov;64(11):1322-7

Escitalopram Found Slightly Better than Citalopram: In an 8-week DB PC study of 134 adults with MDD, MADRS depression scores decreased slightly more in the escitalopram than in the citalopram arm (-22.4 vs. -20.3; P<0.05). There were more treatment responders with escitalopram (76% vs. 61.3%, P<0.01). Adjusted remitter rates were 56% vs. 44%, respectively (P<0.05). Tolerability was similar in both groups. Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder. Moore N, Verdoux H, Fantino B. Bordeaux, France. Int Clin Psychopharmacol. 2005 May;20(3):131-7. Ed: This appears to be a manufacturer-funded study.  They set out to prove excitalopram was better. This highly unusual result needs to be replicated by independent researchers.  Also, very few studies have compared escitalopram to other anti-depressants.  Also, the differences in this study were very small with generic citalopram achieving 91% of the decrease in depression scores that escitalopram obtained.  This difference might fade in a longer study.  

Escitalopram no Better than Citalopram in DB: 491 MDD DB PC escitalopram 10mg/d, escitalopram 20mg/d, citalopram 40mg/d vs. placebo. 10 mg/d escitalopram did as well as 40 mg/d citalopram for depression. Discontinuations due to adverse events for the escitalopram 10 mg/day group was not different from the placebo group (4.2% vs. 2.5%; p = .50), and not different for the escitalopram 20 mg/day group and the citalopram 40 mg/day group (10.4% vs. 8.8%; p = .83). Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. U Nebraska: Burke WJ, Gergel I, Bose A. J Clin Psychiatry 2002 Apr;63(4):331-6

Columbia University Report Claims Lexapro Better: Writers pooled data from three DB PC studies of major depression using escitalopram (10-20 mg/day) and citalopram (20-40 mg/day). The authors conclude that escitalopram treatment was associated with statistically significant improvements in all efficacy measures relative to placebo after 1 week of treatment, whereas citalopram treatment statistically separated from placebo at the end of week 4 (CGI-I and MADRS inner tension) or week 6 (MADRS). Escitalopram treatment also was statistically significantly superior to citalopram treatment at a number of time points. Efficacy comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials. Gorman JM, Korotzer A, Su G. Columbia University. CNS Spectr. 2002 Apr;7(4 Suppl):40-4. Ed: This looks like a biased study in which psychiatrists, probably working closely with the manufacturer.  They seem to be fishing to find any data tilting in favor of Lexapro.  For all we know, there may be other studies out there that the manufacturer wished to suppress because they didn't turn out the desired way.  Such suppression is very common.  In any case, any differences are very minor.

Lexapro Supposedly Better for Depression: In a review of randomized controlled trials of escitalopram (Lexapro) (10-20 mg/day for 8 weeks) versus other antidepressants in therapeutic doses or placebo, 11 of 15 studies were not included due to failing to meet the authors inclusion criteria. Four were accepted (n=1472 patients). The four studies had nine arms, four for escitalopram (n=654), two for citalopram (n=333), one for venlafaxine-XR (n=142) and two for placebo (n=343). Remission rates for escitalopram were superior to placebo (48.7% vs. 37.6%, P=0.003) and citalopram (52.8% vs. 43.5%, P=0.003) but similar to venlafaxine-XR (P=0.97). Evidence based review of escitalopram in treating major depressive disorder in primary care. Einarson TR. University of Toronto, Ontario, Canada. Int Clin Psychopharmacol. 2004 Sep;19(5):305-10. Ed: In all likelihood, every study included was funded by the manufacturer and done by academic psychiatrists depending on receiving pharmaceutical industry support. For decades now, the newest anti-depressant is always the magic bullet, always better than the older, now generic former magic bullets.  With the passage of time, independent researchers have always found the claims of superiority to be without merit.  The very company now selling Lexapro was telling us a few years ago how citalopram (Celexa) was the very best.  Now it's a generic.  I have had several patients doing well on Celexa find that Lexapro did not seem to do as well.

Escitalopram 10mg/d Works in DB: 390 MDD 8 week. Better than placebo. Glasgow. Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Wade A, Michael Lemming O, Bang Hedegaard K. Int Clin Psychopharmacol 2002 May;17(3):95-102

Citalopram > = Sertraline: DB PC 24 week, 323 MDD citalopram 20-60/d vs sertraline 50-150/d. Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline. Citalopram better than placebo on anxiety, but sertraline wasn’t. Sertraline had a trend for higher drop out. UCSD. Stahl SM. Biol Psychiatry 2000 Nov 1;48(9):894-901

Citalopram = Sertraline: DB PC 400 MDD 24 weeks. Sertraline 50-150 (average 84), citalopram 20-60 (aver 38). No difference in any dimension. 90% sertraline vs. 93% citalopram response. Uppsala. A double-blind multicenter trial comparing sertraline and citalopram in patients with major depression treated in general practice. Ekselius L, von Knorring L, Eberhard G. Int Clin Psychopharmacol 1997 Nov;12(6):323-31

Citalopram = Fluvoxamine: DB PC 216 MDD. No difference except citalopram better tolerated, tho no diff in dropout rates. Efficacy and tolerability of citalopram in comparison with fluvoxamine in depressed outpatients: a double-blind, multicentre study. The LUCIFER Group. Haffmans PM, Timmerman L, Hoogduin CA. Int Clin Psychopharmacol 1996 Sep;11(3):157-64

Citalopram = Fluoxetine: DB MDD 8 week. No difference in improvement or rate of side-effects. Citalopram versus fluoxetine: a double-blind, controlled, multicentre, phase III trial in patients with unipolar major depression treated in general practice. Citalopram a little faster and more back pain. Patris M, Bouchard JM, et al. Strasbourg: Int Clin Psychopharmacol 1996 Jun;11(2):129-36

Citalopram = Mirtazapine: DB 270 pt 8 week. No difference at 8 weeks with more nausea on citalopram and more wt. gain with mirtazapine. Mirtazapine was slightly better at the 2 week mark. Efficacy and tolerability of mirtazapine versus citalopram: a double-blind, randomized study in patients with major depressive disorder. Nordic Antidepressant Study Group. Leinonen E, Skarstein J, Behnke K, Agren H, Helsdingen JT. Finland: Int Clin Psychopharmacol 1999 Nov;14(6):329-37

Citalopram = Imipramine: DB 472 MDD 6 week with optional 22 add-on. Anti-depressant benefit equal tho more side-effects, primarily anti-cholinergic, with imipramine. Citalopram and imipramine in the treatment of depressive patients in general practice. A Nordic multicentre clinical study. Rosenberg C, Damsbo N, Fuglum E, Jacobsen LV, Horsgard S. Int Clin Psychopharmacol 1994 Mar;9 Suppl 1:41-8

Citalopram = Amitriptyline in Elderly: >65yo DB 8 weeks. Dry mouth 7% vs 34%. Apparently did use bethanechol. More nausea with citalopram 13% vs 5%. More sleepiness with amitriptyline. Citalopram 20-40mg/d, amitriptyline 50-100/d. Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. Kyle CJ, Petersen HE, Overo KF. Depress Anxiety 1998;8(4):147-53

Citalopram vs Perphenazine for Dementia Psychosis: U Pitt DB PC 85 elderly with hallucinations and agitation. Studied lasted only "up to" 17 days. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Pollock BG, Mulsant BH, Rosen J, Sweet RA, Mazumdar S, Bharucha A, Marin R, Jacob NJ, Huber KA, Kastango KB, Chew ML. Am J Psychiatry 2002 Mar;159(3):460-5. No difference in side-effects in 3 groups and not clear from abstract that citalopram did better although it appears from working of abstract that researchers biased in favor of citalopram.

Intravaginal Ejaculatory Delay for Citalopram & Paroxetine: Study of 30 men with life-long rapid ejaculation. DB PC study 20mg/d each med. 4 week placebo then meds with IELT after paroxetine and citalopram gradually increased from 18 and 21 seconds to approximately 170 and 44 seconds. Measured at home using stopwatches. SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram. Waldinger MD, Zwinderman AH, Olivier B. J Clin Psychopharmacol 2001 Dec;21(6):556-60. J Clin Psychopharmacol 2001 Dec;21(6):556-60

Insulin sensitivity, cortisol secretion and leptin production did not change significantly in depressed women following an 8-week course of citalopram despite substantial improvement in depression scores. Gynecol Endocrinol 2005 Sep;21(3):129-37.

Lack of Orgasms: In a 24-week DB study vs. reboxetine, 39% of sexually active women on citalopram were unable to have orgasms vs. 6% of reboxetine. J Clin Psychopharm 2006 Apr;26(2):121-7.