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Emergence of Antidepressant Induced Suicidality

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Emergence of Antidepressant Induced Suicidality Primary Care Psychiatry, 2000 6:23–28 © LibraPharm Limited Emergence of antidepressant induced suicidality David Healy In the course of a randomised double-blind crossover study comparing the effects of reboxetine and sertraline in a group of healthy volunteers, two volunteers became suicidal on sertraline. This paper describes the charac- North Wales Department of teristics of the reactions experienced by both subjects. These problems Psychological Medicine were associated with a combination of akathisia and disinhibition. Hergest Unit Dysphoric or akathisic responses on their own to either drug did not lead Bangor LL57 2PW, UK to suicidality in this group of subjects. Primary Care Psychiatry 2000; 6:23–28, Copyright © 2000 by LibraPharm Limited Received 22 January 2000; accepted 14 March 2000 Keywords Reboxetine Sertraline Suicide Introduction nomenon in general cleared up on Following the release of fluox- discontinuation of treatment and etine a number of other SSRIs In 1990, Teicher and colleagues re-emerged in a number of cases on appeared on the market including reported on the emergence of suici- re-exposure to the original treat- sertraline and paroxetine. It seems dality on fluoxetine in a group of six ment. In cases where it re-emerged clear that in general these drugs are patients {1}. These reports were fol- there were reports that agents, associated with common profiles of lowed-up by reports from King et al. which theoretically might block the both main effects and side effects. All {2}, Creaney et al. {3}, Rothschild and appearance of a 5HT mediated prob- have received licenses for a similar Locke {4} and Wirshing et al. {5}, lem, were able to minimise or block set of nervous conditions. All pro- among others, reporting other cases the emergence of suicidality on re- duced a set of side effects including where suicidality appeared to emerge exposure. extra-pyramidal side effects, which in individuals taking fluoxetine. Nevertheless, despite a num- are not generally seen with other There were a number of ber of indicators for very clear causal antidepressants {6}. Both sertraline factors associated with these case linkage between the intake of fluoxe- and paroxetine have been associated reports that argued for a strong tine and suicidality, there were also a with reports of akathisia {6,7,8,9,10, causal connection. In general there number of aspects of the reports, 11,12,13}. was consistency across the reports as which argued for some caution in On this basis there would to the time of onset of the problems the interpretation of what was hap- seem therefore to be a possibility following intake of fluoxetine. There pening. One was that some but not that other SSRIs might similarly appeared to be a dose response all of the patients were on other induce suicidality. A meta-analysis of relationship with problems liable to medication. Another was that some trials involving the SNRI milnacipran emerge on a higher dose. There was but not all had lengthy psychiatric compared with SSRIs showed a sig- some agreement as regards the histories with evidence of personal- nificantly increased rate of suicidality probable mechanism leading to the ity problems. It was, in general, less on treatment with SSRIs {14}. A ran- difficulties. This was termed than clear what the description of domised placebo control trial of akathisia, although whether it was this problem emerging in tertiary paroxetine in recurrent major quite the same phenomenon as care centres might mean for the depression showed a higher rate of akathisia traditionally associated with wider world of primary care antide- suicide attempts on paroxetine than neuroleptics was less clear. The phe- pressant prescribing. on placebo in this group of patients 23 Primary Care Psychiatry 2000, Vol 6 No 1 Emergence of antidepressant induced suicidality {15}. These data supplement unpub- dose of the drugs was either 4mgs of When on reboxetine, two sub- lished RCT data from Lilly suggesting reboxetine for the first five days of jects reported becoming depressed. a significantly higher rate of suicide the reboxetine arm with an option to In both cases they likened the expe- attempts in patients taking fluoxe- increase to 4mgs bd if tolerated or rience to post-childbirth baby-blues. tine compared with placebo or other sertraline 50mgs for the first five days Neither of these two subjects or any non-SSRI antidepressants {16,17}. of the sertraline period with an other subject while taking reboxe- Against this background we option to increase to 50mgs bd if tol- tine had suicidal ideation. In con- report the findings from a double- erated. trast, two subjects taking sertraline blind randomised crossover trial of At baseline, subjects com- developed clear suicidal ideation, sertraline and reboxetine in healthy pleted a Karolinska Personality one of which reached extremely seri- volunteers. This was aimed at explor- Questionnaire {18}, a Tridimensional ous proportions. Both these individ- ing modes of action of antidepres- Personality Questionnaire {19}, a uals appear to have had elements of sant drugs on levels of wellbeing and Profile of Mood States (POMS) {20}, a akathisia and emotional blunting but in particular the serenic effect that Positive and Negative Affect Scale other subjects had either akathisia or appears associated with the use of (PANAS) {21}, a Social Adaptation Self emotional blunting without becom- SSRIs which may mediate their ther- Evaluation Scales (SASS) {22} and a ing suicidal. We report on these apeutic effect. BIS-BAS scale {23}. The effects of both cases in more detail, reconstructing drugs in the whole group on mood events from the diaries kept by both scales, personality inventories, side subjects. Methods effect rating scales and other mea- sures will be reported elsewhere Twenty healthy volunteers aged POMS, PANAS and SASS scales Case A between 28 and 52, with a mean age were completed on a daily basis as of 37.8 years, were recruited to a well as a daily diary of impressions of The first case was a 30 year old study comparing reboxetine with the functional and physical effects of woman. She was randomised to sertraline on a range of personality, each drug. Volunteers were actively reboxetine initially. This made her self-report and quality of life mea- encouraged to consult their partners conspicuously relaxed and slightly sures. The study was aimed at estab- or others as to any changes that these sedated on the first day. She lishing the effects of antidepressants others noticed in them over each described the effect as a chill pill. In on levels of wellbeing in subjects not two-week period. A focus group was subsequent days she found normally currently depressed. There were conducted at the end of the study stressing events less stressful. She 9 males and 11 females recruited aimed at establishing whether there described the effect as keeping her from among the administrative, were effects characteristic of either normal temperamental self on the medical and nursing members of the drug. All ratings were done blind. straight and narrow. She had poor North West Wales district general The blind was only broken two weeks sleep but was uncertain if this was hospital psychiatric unit, as well as after the study was completed. owing to childcare or the drug. four others known to members of During the two weeks on what the unit. Ethical permission had turned out to be reboxetine, she been obtained from the North West Results reported dry mouth, sleeplessness, Wales Ethical Committee. Written reduced appetite, nausea and consti- consent to inclusion was obtained A preliminary analysis of the results pation, which she attributed to the from each subject. All volunteers indicates that two-thirds of subjects drug. were free of medical conditions. responded to one or other of the After randomisation to sertra- None were on concurrent drug treat- two drugs but not the other with a line, within the first few days she ment. None had a history of previous ‘better than well’ response. appeared to become avoidant. She psychiatric illness. The two volun- Response appears to have been pre- complained of a stiff jaw (an teers whose experiences are dicted by personality factors similar extrapyramidal side-effect, some reported here have given consent for to those outlined by Joyce in a study variant of which was reported in 45% this information to be reported. of depressed subjects randomised to of the group while on sertraline). Subjects were randomised to either relatively selective noradren- She had a migraine, which she did reboxetine, a selective noradrenaline ergic or serotonergic reuptake not attribute to the drug, along with reuptake inhibitor, or sertraline, a inhibitors {24}. The group also nausea, malaise, restlessness, agita- selective 5HT reuptake inhibitor, in a showed changes on the KSP that tion, anxiety, vivid emotions, racing crossover design so that a propor- have been reported in depressed thoughts and ruminations, which tion received reboxetine for two patients following SSRIs {25}. Finally she did attribute to the drug. weeks followed by a two week drug in the group as a whole a greater From the end of the first week free period and thereafter sertraline number of subjects expressed a she was reported by colleagues to be for two weeks or alternatively sertra- preference for sertraline than for somewhat restless and fidgety. To line followed by reboxetine. The reboxetine. some she appeared akathisic but not 24 Primary Care Psychiatry 2000, Vol 6 No 1 Emergence of antidepressant induced suicidality so clearly that everyone would lessness of her legs. She said that she suddenly decided she should go and notice. She recognised her restless- was not doing much work, that she throw herself in front of a car, that ness and had found that with a couldn’t cope with anyone’s emo- this was the only answer.
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