Mental health series: Pharmacists in suicide prevention…Where do they fit?

Hayley Gorton
Hayley Gorton

DO pharmacists in public health=pharmacists in suicide prevention? A Blog Series…

In the first blog in this series, I described the reduction of suicide as a worldwide public health priority; along with medical, social and demographic factors which may contribute to increased risk of suicide. In this instalment, I will discuss the contribution of medication to suicide both as a method of suicide (poisoning); and as potential modifiers of suicide risk.

In 2014, there were 3,346 poisoning deaths (accidental, suicide abuse & dependence) in England and Wales. Overall, poisoning deaths were 2.5 times more common in men than women. In men, 15% of poisonings were suicides and in women this was 27% [1]. This contravenes the general trend of suicide deaths being more common in men, [2] and reinforces the need for suicide awareness in both genders.

One third of poisoning deaths mentioned multiple specific drugs on the death certificate, and alcohol was implicated in a similar proportion. Opiates were the most frequently recorded drugs involved in poisoning, of which 952 deaths involved heroin or morphine.

Poisoning deaths from tramadol increased from 132 in 2010, to 240 in 2014 [1]. This prompted a review by the Advisory Council for the Misuse of Drugs (ACMD) which resulted in the recommendation that tramadol be rescheduled under Schedule III of the Misuse of Drugs Act [3]. Therefore, from June 2014, tramadol was subject to more stringent prescribing and dispensing controls, in an attempt to reduce diversion and misuse (both intentional and unintentional). At the same time, zoplicone and zolpidem where also classified as controlled drugs. The involvement of these drugs in poisoning deaths increased by 50% in the years 2010 to 2014.

Of other commonly dispensed medications, antidepressants were involved in 517 poisoning deaths [1]. There is increasing concern about diversion of pregablin and gabapentin, especially as drugs of misuse in prisons and in 2013, there were 41 mentions of these drugs on death certificates [4, 5].

In 1998, a restriction in paracetamol pack size was enforced (16 in non-pharmacy outlets and 32 in pharmacies). Although paracetamol-related poisonings did reduce [6], they had remained relatively stable in recent years and the 200 deaths in 2014 was a 20% decrease on 2013.

Conversely, there was a similar increase in deaths involving co-codamol over the same time frame [1]. Last month, a study which explored sales of multiple paracetamol-containing products from non-pharmacy outlets, was published. Alarmingly, 58% of retailers sold more than the recommended two packs of 16 paracetamol, and a similar percentage sold a paracetamol-containing cold and flu remedy with this quantity [7].
Prescribers, pharmacists and patients need to be aware of the overdose potential for medicines. On the other side of the coin, the potential for medicines to influence or mitigate suicide risk must also be borne in mind.

Given that there are many factors which might contribute to an individuals’ suicide risk, it is unsurprising that there is no ‘treatment’, as such, for suicidality. Naturally, one would expect that if underlying mental health conditions are treated, this could indirectly reduce suicide risk. Some medicines have been associated with reduced suicide risk:

Clozapine- the reduction of suicidal behaviour is a labelled indication of this atypical antipsychotic [8] and the InterSePT trial showed a modest reduction in risk of suicide compared to olanzapine [9]. However, in a report of adverse events reported on the MHRA yellow card system, clozapine had the highest suicide rate [10].

Lithium-a protective effect was suggested in a meta-analysis of 22 trials [11] however it is uncertain whether the trials included were comparable, particularly in relation to the underlying illness [12].

Ketamine- the ‘buzz’ drug in the media at the moment. It has been suggested to be useful in the reduction of suicidal ideation before traditional antidepressant action begins [8]. The investigative use of ketamine has only been in a small number of patients. There were just 201 patients in 9 trials included in a recent meta-analysis and 7 trials mentioned unpublished data on suicidality, which suggested a reduction in suicidality at 1 and 3 days after first ketamine dose [13]. However, in a small trial of ten people, two experienced suicidal ideation on exposure to ketamine [14].

Some medicines have, however, also been linked to increased suicide risk. These are often identified through ad hoc reports, such as via the Medicine and Healthcare Products Regulatory Agency (MHRA) yellow card system, or epidemiology studies. This is because although suicide occurs all too frequently, there are not enough people in pre-marketing clinical trials to detect suicide. Furthermore, interventions would be made in these trials if people were considered at risk.

In 1990, Teicher et al published a series of six reports which suggested increased risk of suicidal ideation when people first began using the antidepressant fluoxetine [15]. In a review of 24 randomised controlled trials, involving 43,892 individuals, of antidepressants by the American Food & Drug Administration (FDA); only one trial showed statistical significance for suicidal behaviour and no suicide deaths occurred [16].

However, this culminated in the issue of a warning of increased risk in children and young people and antidepressants had to be labelled to reflect this [17]. In 2007, the analysis was extended to the adult population and no increased risk was found in adults over age 24, and a protective effect was suggested in those over 65 [18]. The mandatory warnings were updated to reflect this.

A recent meta-analysis of clinical trial data, much of which was found from trial reports rather than published material, showed an increased risk of suicidality in adolescents and children [19]. However, it should be noted that suicidality outcomes may have variable suicide intent, which might be difficult to determine in children.

The possible influences of psychotropic medication on suicide risk must be considered in relation to underlying risk associated with the illness being treated. Certain physical health conditions are also thought to increase suicide risk. This must be borne in mind when interpreting possible risks associated with non-psychotropic medication. Occasionally, spontaneous reports link certain medicines with a suicide death.

Perhaps the most often cited of these drugs are isotretinoin and varenicline. In 2014, an expert review could not conclude that there was or wasn’t a risk associated with isotretinoin [20], independent of risk conferred by the psychological influence of severe acne. Varenicline, the smoking cessation drug, carries warnings for suicidal ideation. An ongoing study is being led by the manufacturers, in attempt to review this warning [21].

Efavirenez, isotretinoin and mefloquine are the three non-psychotropic medicines most frequently reported on the yellow card system in relation to suicide [10]. Spontaneous reports are imperative to recognise possible drug safety signals, but it is often useful to quantify risk using observational studies. We therefore conducted a systematic review to understand which non-psychotropic medicines have been investigated and what associations have been made. Seven groups of medicines were identified. No increased risk was associated with cardiovascular medication, quinolone antibiotics, montelukast or varenicline. Whether antiepileptic drugs, isotretinoin or glucocorticoids increase suicide risk is still unknown and requires more research [22]. Our full review can be freely accessed here.

An awareness of medication which might influence or be involved in suicide deaths is important in day-to-day provision of healthcare. This must, however, be considered alongside other risk factors for suicide in a holistic manner.

Help and advice
If you need to direct patients, customers, colleagues, friends or family for support; the following helplines are available:
Samaritans: 116 123
Mind: 0300 123 3393
Childline: 0800 1111 (children)
Papyrus: 0800 068 4141 (teenagers and adults)
Hayley Gorton MRPharmS MPharm
@hayley_gorton @meds_safety @MPSPharmPrac
The views expressed in this are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health.

Hayley Gorton is a community pharmacist and a PhD student at Manchester Pharmacy School involved in suicide, medication safety, and pharmacoepidemiology research.

Follow Hayley @hayley_gorton

References
[1] Office for National Statistics. Deaths related to drug poisoning in England and Wales, 2014 registrations. Newport: Office for National Statistics. 2015.

[2] World Health Organization. Preventing Suicide: A global imperative Geneva: WHO, 2014.

[3] ACMD. ACMD Consideration of Tramadol. 2013.

[4] Drugscope. Down a stony road: The 2014 DrugScope Street Drug Survey [2015; 14 Oct 2015].

[5] Office for NationalStatistics. Drug-related deaths where gabapentin and pregabalin were mentioned on the death certificate, England and Wales, 1999-2013. Newport: Office for National Statistics. 2014.

[6] Hawton K, Bergen H, Simkin S, Dodd S, Pocock P, Bernal W, et al. Long term effect of reduced pack sizes of paracetamol on poisoning deaths and liver transplant activity in England and Wales: interrupted time series analyses. BMJ. 2013;346:f403.

[7] Molloy P, Chambers R, Cork T. How well are national guidelines relating to the general sales of aspirin and paracetamol, adhered to by retail stores: a mystery shopper study. BMJ Open. 2016;6(1).

[8] Griffiths JJ, Zarate Jr CA, Rasimas JJ. Existing and Novel Biological Therapeutics in Suicide Prevention. Am J Prev Med. 2014;47(3S2):S195-S203.

[9] Meltzer HY, Alphs L, Green AI, Altamura AC, Anand R, Bertoldi A, et al. Clozapine Treatment for Suicidality in Schizophrenia: International Suicide Prevention Trial (InterSePT)FREE. Arch Gen Psychiatry. 2003;60(1):82-91.

[10] Thomas KH, Martin RM, Potokar J, Pirmohamed M, Gunnell D. Reporting of drug induced depression and fatal and non-fatal suicidal behaviour in the UK from 1998 to 2011. BMC Pharmacol Toxicol. 2014;15(54).

[11] Tondo L, Hennen J, Baldessarini R. Lower suicide risk with long-term lithium treatment in major affective illness: a meta-analysis. Acta Psychiatr Scand. 2001;104:163-72.

[12] Burgess S. Commentry: Long term lithium treatment lowers suicide risk in major affective disorder. Evid Based Med. 2002;7:p 50.

[13] Xu Y, Hackett M, Carter G, Loo C, Gálvez V, Glozier N, et al. Effects of low-dose and very low-dose dose ketamine among patients with major depression: a systematic review and meta-analysis. International Journal of Neuropsychopharmacology. 2015 doi: 10.1093/ijnp/pyv124

[14] Niciu MJ, Grunschel BD, Corlett PR, Pittenger C, Bloch MH. Two cases of delayed-onset suicidal ideation, dysphoria and anxiety after ketamine infusion in patients with obsessive-compulsive disorder and a history of major depressive disorder 2013 [7:[651-4].

[15] Teicher M, Glod C, Cole J. Emergence of intense suicidal preoccupation during fluoxetine treatment. Am J Psychiatry. 1990;147(2):207-10.

[16] Hammad T. Review and evaluation of clinical data: relationship between psychotropic drugs and pediatric suicidality. Rockville (MD): US Food and Drug Administration, 2004.

[17] FDA. Worsening Depression and Suicidality in Patients Being Treated with Antidepressants 2004 [Accessed 20 Jan 2015]

[18] Laughren TP. Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee (PDAC). [2006; cited Dec 08].

[19] Sharma T, Guski LS, Freund N, Gøtzsche PC. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. BMJ. 2016;352.

[20] Authority MaHR. Review of isotretinoin and psychiatric adverse reactions. MHRA, 2014

[21] Varenicline for smoking cessation United Kingdom: Consumers’ Association. [ 2008; accessed 20 Jan 2015].

[22] Gorton HC, Webb RT, Kapur N, Ashcroft DM. Non-psychotropic medication and risk of suicide or attempted suicide: a systematic review. BMJ Open. 2016;6(1).

 

This article has kindly been sponsored by Pharmacy Management. This article is part of our focus on mental health through December and into January in preparation for the upcoming conference on mental health. To view the excellent agenda click on the image above.

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