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1992 6: 334J PsychopharmacolMalcolm Peet

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The prevention of suicide in patients with recurrent mood disorder

Malcolm Peet

Department of Psychiatry, Northern General Hospital, Sheffield S5 7AU, UK

Recurrent mood disorder carries a risk of suicide of 15%. Patients who do commit suicide have often received

inadequate antidepressant or prophylactic lithium treatment. Long-term treatment with lithium normalizes

the excess mortality associated with recurrent mood disorders, including that from suicide.A reduced

availability of the most lethal methods of suicide may contribute epidemiologically to a reduced rate of suicide,and therefore the differences in overdose toxicity between antidepressants may be pertinent. Education of

mental health workers regarding the effective treatment of mood disorders can help to reduce the rate of

suicide. Patient education and psychological support can lead to improved compliance with prophylacticmedication and early detection of relapse, but more formal psychotherapy does not appear to be helpful.

Specialized mood disorder clinics lead to better patient care than is possible in a routine psychiatric out-patient

clinic.

Key words: suicide; recurrent mood disorder; lithium; antidepressants; education; specialist clinics

Introduction

It is well recognized that patients with recurrent mooddisorder have a substantially increased risk of death bysuicide (Guze and Robins, 1970; Lee and Murray, 1988;Kiloh,Andrews and Neilson, 1988). Weeke, Juel andVaeth

(1987)studied two

patientcohorts, one before

and one during the tricyclic antidepressant era, whowere followed up for an average of 4.5 years. Both

groups showed a high rate of death from suicide and

accident, with no significant difference between the two

groups. This had led to the pessimistic conclusion thatthe introduction of modern psychotropic drugs has hadlittle real impact on the outcome of recurrent mooddisorder. However, most studies have made no attemptto examine the adequacy or otherwise of pharmacologicaltreatment during the follow-up period. It is well

recognized that antidepressant treatment is frequentlyinadequate.

In view of the continuing high suicide mortality, despitethe availability of modern pharmacological treatment, itis important to examine the reasons for this and to suggeststeps that could be taken to reduce suicide mortality. Thisreview will examine the evidence for the effect of adequatepsychotropic medication on suicide mortality, and will

emphasize the usefulness of lithium clinics and mooddisorder clinics as a means of ensuring that treatment isadministered properly. Other possible ways of reducingsuicide mortality, such as education of patients and

general practitioners on the proper treatment of mood

disorder, and the reduction in availability of hazardousmethods of self-harm will also be discussed.

The effect of antidepressanttreatment on the rate of suicide

The effect of antidepressant treatment on the risk ofsuicide has been examined in two ways:

1. by looking at the treatment that patients were receivingat the time of committing suicide;

2. by studying mortality from suicide and other causesin a cohort of patients who have received adequatepharmacological treatment.

Often, depressive episodes do not come to medical

attention, and when they do so they are under-recognizedand undertreated. Antidepressant medication is

commonly used inadequately. In a survey of patients inthe community with major depressive disorder, Keller etal. (1982) found that only 34% had received

antidepressants for at least 4 weeks and only 12% were

given doses of tricyclic antidepressants that exceeded

150 mg daily.In a study of depressed patients treated in general

practice, Johnson (1973) found that only 25% had been

prescribed > 75 mg amitriptyline daily or its equivalent.Even patients who are referred for psychosurgery becauseof chronic intractable depression have commonly had

Journal of Psychopharmacology 6(2) Supplement (1992) 334-339 1992 BritishAssociation for Psychopharmacology

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prolonged periods of inadequate treatment with anti-

depressant drugs (Bridges, 1983).It is, therefore, not surprising that several studies have

shown successful suicide to be associated with inadequatepharmacological treatment of the underlying mooddisorder. Myers and Neal (1978) found that 63% of

psychiatric patients in their series who committed suicidehad seen a doctor within 1 month beforehand. However,of 44 patients with a known diagnosis of depressive illnessfor whom adequate information was available, only fivewere taking antidepressant medication in a dose

approaching that recommended by the manufacturer, and

only one patient was receiving ECT.Modestin (1985) reported a series of 61 suicides who

met diagnostic criteria for depressive disorder. He foundthat less than half of the patients had been treated with

antidepressant drugs and only one fifth had received an

adequate dose, which was defined rather modestly as150 mg of a tricyclic antidepressant/dayor a comparable

dose of another antidepressant. In a subsequent study,Modestin and Schwarzenbach (1992) compared thetreatment received by 64 psychiatric patients whocommitted suicide within 1 year of hospital discharge withthat of a matched patient control group who did notcommit suicide. Of the patients who committed suicide,one third had no longer been in treatment and a furtherthird had received therapy without psychotropic medica-tion.At the time of suicide, or at the corresponding timefor the control group, a significantly higher proportionof controls had been receiving drug treatment,particularly lithium. No patient on lithium in this study

committed suicide.Schou and Weeke (1988) examined a series of 92

Danish manic-depressive patients who committed suicide

following a previous psychiatric admission, with

particular regard to the adequacy of prophylactic orcontinuation treatment. They concluded that 30% of the

suicides were associated with inadequate treatment, orno continuation or prophylactic treatment, even thoughthis was indicated. Thus, these suicides might have been

prevented by adequate pharmacotherapy.In view of the widespread undertreatment of depression,

it is perhaps not surprising that epidemiological studiesof the outcome of depression have not shown any strikingimprovement since the introduction of antidepressantmedication. Moreover, the high rate of undertreatmentfound in patients who successfully commit suicide suggeststhat adequate treatment will lower suicide mortality.

Prophylactic therapy andthe rate of suicide

Even before the introduction of modern psychotropicdrugs, it was recognized that both suicidal and general

mortality from depressive illness is reduced by effectivetreatment with ECT (Huston and Locher, 1948; Ziskind,Somerfeld-Ziskind and Ziskind, 1945). More recentevidence suggests that the excess mortality in affectivedisorder is now primarily related to suicide and accidentaldeath rather than to increased cardiovascular and other

mortality,which used to be more prominent (Eastwood

et al., 1982). Increased awareness of the frequentrecurrence and chronicity of mood disorder hasstimulated research into the effect of long-term

prophylactic treatment on mortality.

Coppen et al. (1990, 1991) studied 103 patientsattending a lithium clinic over 11years. Only 10 patientstreated with lithium died, compared to an expectednumber of 18.31 in the general population, a differencewhich almost reached statistical significance. There wereno deaths from suicide in the lithium-treated group.

Muller-Oerlinghausen et al. (1991) studied 813 patientsattending four lithium clinics who had been receiving

lithium for periods ranging between 6 months and 20years. They found that the cumulative mortality duringtreatment with lithium did not differ significantly fromthat of a corresponding normal population. Both of thesestudies suggest that the excess mortality associated withrecurrent mood disorder, particularly from suicide, isnormalized by affective lithium treatment carried out inthe setting of a specialized lithium clinic.

Contrasting results were reported by Vestergaard and

Aagaard (1991), who found that mortality in a group of

patients treated with lithium over a 5-year period was fourtimes greater than that expected in a normal population.This excess occurred

for both suicide andnatural

causes,including cardiovascular disease. Norton and Whalley(1984) obtained mortality data on 791 patients treatedwith lithium in various settings throughout south-eastScotland and found a standardized mortality rate of 2.83,with excess mortality primarily attributable to suicide butalso to cardiovascular disease. Most patients who diedof cardiovascular disease had clinical evidence of

cardiovascular problems before treatment with lithium.It has been argued that the discrepancy in the findings

between these two pairs of studies may be due todifferences in the patient population. The studies showingnormal mortality during treatment with lithium involved

patients who were well established in a programme oflithium treatment and were thus especially compliant(Vestergaard andAagaard, 1991). Of greater importancemay be the fact that patients in the two positive studieswere treated under very strictly controlled conditions ina lithium clinic. In the clinic run by Coppen and

colleagues, patients are not pre-selected on the basis of

compliance and yet the clinic achieves a very highcompliance rate, low drop out rate and substantialamelioration of affective morbidity (Coppen andAbou-

Saleh, 1988). In contrast,Aagaard and Vestergaard (1990)



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report that 42% of the patients attending their clinicdiscontinued lithium treatment at least once within a

2-year period and the clinical outcome was correspondinglypoor.

Few systematic data are available on the effect of other

psychotropic drugs on the rate of suicide. While

antidepressantsand

carbamazepinecan both be effective

prophylactic agents, the effect of such prophylactictreatment on the risk of suicide has not been adequatelyevaluated. Injections of low dose flupenthixol have been

reported to reduce suicidal behaviour in patients with a

personality disorder and a history of repeated suicide

attempts (Montgomery et al., 1979). High doses of

neuroleptic drugs appear to be associated with anincreased risk of suicide (Cheng et al., 1990; Hogan and

Awad, 1983), possibly due to the induction of akathisia,which appears to be a risk factor for suicide (Shear,Frances and Weiden, 1983). In general, doses of

neuroleptic drugs that are sufficient to cause

extrapyramidal side effects, such as akathisia, are bestavoided in depressive disorders.

Non-pharmacological interventions

The clinical predictors of suicide are so broad that manyfalse-positives are included. However, attempts to narrow

or raise the threshold of these criteria result in false-

negative predictions so that many suicidal deaths aremissed (Kreitman, 1989). Nevertheless, it is customaryto hospitalize patients whom the psychiatrist considersto be at a

high risk from suicide, regardless of howinaccurate this prediction may be. However, hospitaladmission and special observation can be counter-

productive, leading to an increased risk of suicide attemptin some individuals (Pauker and Cooper, 1990). Manypotentially suicidal patients can be managed in aneffective community care programme without an increasedincidence of suicide (Hoult, 1986).

Studies of the psychotherapeutic after-care of patientswho have attempted suicide have produced disappointingresults. Such studies generally compare two differentmodes of intervention, because of the ethical problemsof allocating patients to a control group, with nointervention. Comparisons of different psychosocialinterventions have failed to show any real advantage forone type of intervention over another (Moller, 1989).Thus, out-patient counselling has no advantage over care

by general practitioners (Hawton et al., 1987), intensivecase work from a social worker is no better than a routine

after-care service (Gibbons et al., 1978) and behaviour

therapy is no better than insight-orientated therapy asassessed by repeat suicide attempts, though symptomaticimprovement was greater in the group undergoingbehavioural therapy (Liberman and Eckman, 1981).

Most patients included in such studies are not sufferingfrom a major depressive disorder. It is possible that

cognitive therapy could help to prevent a relapse of majordepressive disorder and thereby reduce the risk of suicide,but this remains to be established (Blackburn, Euson and

Bishop, 1986). Interpersonal psychotherapy used asan

adjunctto

imipramineseems to

delay depressiverelapse, but does not prevent it (Frank, Cupfer and Perel,1989). The possible role of non-statutory counsellingand befriending services, such as the Samaritans has alsobeen evaluated.An initial report which appeared to show

that the Samaritans were responsible for a fall in thenational suicide rate (Bagley, 1968), was subsequentlyrebutted (Barraclough and Jennings, 1977; JenningsBarraclough and Moss, 1978), and it is now acceptedthat such a service, while valuable in helping somedistressed people, does not affect the actual rate ofsuicide.

The development of trusting relationships between the

patient and suitably experienced, sympathetic andavailable professional staff appears to be central toeffective programmes of suicide prevention. Staff shouldbe available at times of personal crisis and not only atfixed appointments.

Educational issues

Because of the widespread pharmacological under-treatment of mood disorder, there is a clear role for

education of both psychiatrists and general practitioners

regardingthe

proper management of patientswith

sucha condition. Rutz, Knorring and Walinder (1989) reportedon the effects of a systematic educational programme for

general practitioners in Sweden, which resulted in betteridentification and more accurate treatment of depressivedisorders. The rate of suicide fell during the yearafter the educational programmes were introduced.An

educational programme for naval instructors on aspectsof attempted suicide resulted in a decreased rate of

parasuicidal behaviour (McDaniel, Rock and Grigg,1990).Education of patients is also important for those

taking long-term prophylactic medication. There is

evidence that provision of a standard educational

programme for patients (video tape lecture and written

hand-out, together with one-to-one discussion of theeducational material) results in a substantial improvementin patients knowledge of their treatment and its hazards

(Peet and Harvey, 1991), as well as improved tablet

compliance (Harvey and Peet, 1991). Proper patienteducation forms an essential part of the work of a

mood disorder clinic, which improves the trust between

patients and staff, as well as the compliance withmedication.



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Availability of hazardous methodsfor suicide attempts

There is evidence that the availability of lethal methodsfor suicide affects not only the rate of suicide for that

method, but can also have an effect on the overall rate

of suicide. The best known example is the decline in thespecific and total rate of suicide which was associated withthe detoxification of domestic gas in the UK(Lowe etal., 1981). Recently, there has been a similar report from

Japan, which found a reduction in the use of domestic

gas for suicide after it was detoxified, with no evidencethat potential suicides used alternative methods (LesterandAbe, 1989). Emission controls on car exhausts in theUSA (Clarke and Lester, 1987) and the restriction of gunownership in the USA (Lester, 1988) both correlate withthe rate of suicide by these means. Kreitman (1989) arguedthat the evidence for the reduction in the overall rate of

suicide resulting from the restriction of hazardous methodsof suicide is sufficient for psychiatrists to support thelimitation of potentially lethal means of self damage,including the use of less toxic drugs where possible.

Lithium overdose is seldom used as a means for suicide,

possibly because of the effectiveness of lithium therapyor because patients are educated about its toxicity so that

parasuicidal behaviour involving lithium is relativelyuncommon. However, there has been considerable focus

on the relative toxicity of the antidepressant drugs whichare commonly prescribed during depressive episodes whenthe risk of attempting suicide is enhanced. The availableevidence on overdose toxicity clearly shows that the older

tricyclic antidepressants, such as dothiepin and amitripty-line, are substantially more toxic in overdose than thesecond generation antidepressants, such as lofepramine,trazodone and the specific 5-hydroxytryptamine (5-HT,serotonin) re-uptake inhibitors (Henry, 1989). Overdosesof antidepressant drugs are commonly taken by patientsattempting suicide, and it would seem prudent for

psychiatrists to use the relatively less toxic agents for thetreatment of acute depressive episodes. There may also be

advantages in using newer less toxic drugs, such as the

specific 5-HT uptake inhibitors which have been shown tobe effective prophylactically (Montgomery et al., 1988),but there is as

yetno evidence that

long-termtreatment

with these agents leads to a reduced rate of suicide.

Mood disorder clinics

Specialist lithium clinics have been in operation since the1960s and have been established in increasing numbers.Some clinics are aimed primarily at optimizing lithium

treatment, whereas others are mood disorder clinics which

offer a broader spectrum of treatment (Fieve and

Peselow, 1987).

Such clinics have considerable advantages. First, theyoffer a centre of expertise, not only for treatment with

lithium, but also for other aspects of the diagnosis andtreatment of affective disorders, such as the managementof resistant depression and the use of non-pharmacologicaltreatments, including cognitive therapy. Patients, therefore,receive the best

possiblecare under

optimalconditions

from a multidisciplinary team. The clinics facilitate theeducation of patients and their relatives, as well as

professionals in the process of training. The more

developed clinics use specific monitoring systems with

rating scales for mood disorder and side effects, which

produce valuable longitudinal data.Arrangements aremade for the monitoring of lithium levels and otherbiochemical variables in a systematic fashion so thatvaluable information does not get lost or delayed. The

clinic, with regular staff skilled in the management ofaffective disorder, provides a contact point for patientsand relatives who may be worried about early signs of

relapse or lithium intoxication. Well-run clinics will havean established contact and follow-up system for any

patient who may default from an appointment.Patients with long-term mood disorder need appropriate

psychological support, as well as adequate pharmaco-logical treatment. The mood disorder clinic is a goodfocus for support groups and self-help groups (Rook,1987). The cost-effectiveness of a lithium clinic, includingreduced hospitalization costs and avoidance of the lossof productivity, has also been highlighted (Peselow and

Fieve, 1987).

Conclusion

Affective disorder still carries a poor long-term prognosis,including a substantial risk of suicide, despite advancesin modern psychopharmacological treatment. There ismuch evidence to suggest that affective disorder is widelyundertreated, both during the acute phase and

prophylactically. Adequate treatment of recurrentaffective disorder, both in the short- and long-term,can bring about a substantial reduction in mortalityfrom suicide. Education of practitioners and the establish-ment of specialist lithium clinics or mood disorder

clinics where skilled treatment and monitoring can beprovided, may be instrumental in reducing the rate ofsuicide.

Address for correspondence

M. Peet

Department of PsychiatryNorthern General HospitalSheffield S5 7AU

UK



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