On 2015 Oct 27, Peter Gøtzsche commented:

The authors report that escitalopram was significantly more effective than citalopram but caution against the “potential for overestimation of treatment effect due to sponsorship bias.” Indeed. Both substances were patented by Lundbeck, and the rejuvenated “me-again” drug, escitalopram, is merely the active half of the “old me” stereoisomer drug, citalopram.

One would not expect a molecule to be better than itself. I therefore suggest that the Cochrane review mention the results of a 2012 meta-analysis (1), also in the abstract and plain language summary. Independent researchers confirmed the Cochrane review’s findings that escitalopram was better than citalopram in head-to-head trials. All seven trials found this, apart from the single one that was not sponsored by Lundbeck or its affiliates. These researchers also did an indirect comparison of the two drugs based on 10 citalopram and 12 escitalopram placebo controlled trials (1), and now the effect of “me-again” and “old me” was very similar (odds ratio 1.03; 0.82 to 1.30).

Usually, direct comparisons are more reliable than indirect comparisons, but the drug industry routinely distorts its research to such an extent (2) that the indirect comparisons are sometimes the most reliable ones, which I believe is the case here. Lundbeck did not have any particular incentive to manipulate its placebo controlled studies more with escitalopram than with citalopram.

The Cochrane authors note that cost-effectiveness information is also needed in the field of antidepressant trials. Indeed. Even if we take Lundbeck’s results in its head-to-head trials at face value, there is no meaningful difference between the two versions of the drug. In one of Lundbeck’s own meta-analyses, the difference after eight weeks was 1 on a scale that goes up to 60 (2,3), which is totally irrelevant (4).

When I checked the Danish prices in 2009, Cipralex (escitalopram) cost 19 times as much for a daily dose as Cipramil (citalopram). This enormous price difference should have deterred the doctors from using Cipralex, but it didn’t. The sales of Cipralex were six times higher in monetary terms than the sales of citalopram both at hospitals and in primary care. I have calculated that if all patients had received the cheapest citalopram instead of Cipralex or other SSRIs, Danish taxpayers could have saved around €30 million a year, or 87% of the total amount spent on SSRIs.

1 Alkhafaji AA, Trinquart L, Baron G, et al. Impact of evergreening on patients and health insurance: a meta analysis and reimbursement cost analysis of ci¬talopram/escitalopram antidepressants. BMC Med 2012;10:142.

2 Gøtzsche PC. Deadly medicines and organised crime: How big pharma has corrupted health care. London: Radcliffe Publishing; 2013.

3 Gorman JM, Korotzer A, Su G. Efficacy comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials. CNS Spectr. 2002; 7(4 Suppl. 1): 40–4.

4 Leucht S, Fennema H, Engel R, et al. What does the HAMD mean? J Affect Disord 2013;148:243-8

On 2015 Oct 27, Peter Gøtzsche commented:

The authors report that escitalopram was significantly more effective than citalopram but caution against the “potential for overestimation of treatment effect due to sponsorship bias.” Indeed. Both substances were patented by Lundbeck, and the rejuvenated “me-again” drug, escitalopram, is merely the active half of the “old me” stereoisomer drug, citalopram.

One would not expect a molecule to be better than itself. I therefore suggest that the Cochrane review mention the results of a 2012 meta-analysis (1), also in the abstract and plain language summary. Independent researchers confirmed the Cochrane review’s findings that escitalopram was better than citalopram in head-to-head trials. All seven trials found this, apart from the single one that was not sponsored by Lundbeck or its affiliates. These researchers also did an indirect comparison of the two drugs based on 10 citalopram and 12 escitalopram placebo controlled trials (1), and now the effect of “me-again” and “old me” was very similar (odds ratio 1.03; 0.82 to 1.30).

Usually, direct comparisons are more reliable than indirect comparisons, but the drug industry routinely distorts its research to such an extent (2) that the indirect comparisons are sometimes the most reliable ones, which I believe is the case here. Lundbeck did not have any particular incentive to manipulate its placebo controlled studies more with escitalopram than with citalopram.

The Cochrane authors note that cost-effectiveness information is also needed in the field of antidepressant trials. Indeed. Even if we take Lundbeck’s results in its head-to-head trials at face value, there is no meaningful difference between the two versions of the drug. In one of Lundbeck’s own meta-analyses, the difference after eight weeks was 1 on a scale that goes up to 60 (2,3), which is totally irrelevant (4).

When I checked the Danish prices in 2009, Cipralex (escitalopram) cost 19 times as much for a daily dose as Cipramil (citalopram). This enormous price difference should have deterred the doctors from using Cipralex, but it didn’t. The sales of Cipralex were six times higher in monetary terms than the sales of citalopram both at hospitals and in primary care. I have calculated that if all patients had received the cheapest citalopram instead of Cipralex or other SSRIs, Danish taxpayers could have saved around €30 million a year, or 87% of the total amount spent on SSRIs.

1 Alkhafaji AA, Trinquart L, Baron G, et al. Impact of evergreening on patients and health insurance: a meta analysis and reimbursement cost analysis of ci¬talopram/escitalopram antidepressants. BMC Med 2012;10:142.

2 Gøtzsche PC. Deadly medicines and organised crime: How big pharma has corrupted health care. London: Radcliffe Publishing; 2013.

3 Gorman JM, Korotzer A, Su G. Efficacy comparison of escitalopram and citalopram in the treatment of major depressive disorder: pooled analysis of placebo-controlled trials. CNS Spectr. 2002; 7(4 Suppl. 1): 40–4.

4 Leucht S, Fennema H, Engel R, et al. What does the HAMD mean? J Affect Disord 2013;148:243-8