Popular antidepressant associated with a dramatic increase in suicidal thoughts amongst men
15 October 2009
Nortriptyline has been found to cause a ten-fold increase in suicidal thoughts in men when compared to its competitor escitalopram. These findings are published in the open access journal BMC Medicine today. The research was carried out by Dr Nader Perroud from the Institute of Psychiatry (IoP) at King's, by analysing data from the European Commission funded Project, GENDEP, led by Professor Peter McGuffin and Dr KJ Aitchison at the IoP’s MRC SGDP Centre.
Dr Perroud said: “Suicidal thoughts and behaviours during antidepressant treatment have prompted warnings by regulatory bodies. The aim of this analysis was to investigate the emergence and worsening of suicidal thoughts during treatment with two different types of antidepressant. The reason that we conducted this was that suicidal ideation occurring during antidepressant treatment has been a major international concern.”
Both escitalopram and nortriptyline have their effect through the mood modulating neurotransmitter systems. The former is a selective serotonin reuptake inhibitor (SSRI), preventing serotonin from re-entering the cell and thereby prolonging its effect on nerve synapses. The latter is a tricyclic antidepressant that inhibits the reuptake of noradrenaline, and to a lesser extent, that of serotonin.
The study was carried out on 811 individuals with moderate to severe unipolar depression. Whilst an overall trend in reduction of suicidal thoughts was observed, men who took nortriptyline were found to have a 9.8-fold increase in emerging suicidal thoughts and a 2.4-fold increase in worsening suicidal thoughts compared to those who took escitalopram. The worst period for suicidal thoughts was in week 5 of treatment. Retirement and history of suicide attempts predicted worsening of suicidal ideation on treatment.
Dr Aitchison commented: 'This study shows a peak in suicidal ideation slightly later - at week 5 - in the course of treatment than most clinicians previously thought occurred. This is important for monitoring patients for risk of suicide on treatment. Moreover, in this study, retirement and history of suicide attempts predicted treatment-worsening of suicidal ideation. In the context of the current socio-economic climate, this deserves serious consideration.'
Dr Perroud adds: 'Our findings that treatment-emerging and worsening suicidal thoughts may also be associated with psychomotor activation triggered by antidepressants need to be investigated in future studies. The study also refutes the idea that newer antidepressants such as the SSRIs are worse than older medications in terms of increasing suicidal thoughts.'
Dr Aitchison concludes: 'Further research investigating suicidal thoughts and behaviours on treatment with antidepressants and other medications is indicated.'
Suicidal ideation during treatment of depression with escitalopram and nortriptyline in Genome-Based Therapeutic Drugs for Depression (GENDEP): a clinical trial can be accessed here: http://www.biomedcentral.com/bmcmed/
For further information about GENDEP: http://gendep.iop.kcl.ac.uk/results.php
Dr Nader Perroud can be contacted at: Nader.Perroud@hcuge.ch