54 Pharmacological and other biological treatments of suicidal individuals

Due to the role of depressive disorders, as the most frequent cause of suicidal behaviour, antidepressants have the most prominent place in psychopharmacological prevention of suicidal behaviour. Based on clinical experience, antidepressants reduce suicidality in association with the reduction of depressive symptoms, and it is assumed that suicidal behaviour is also reduced as a consequence. However, based on the results of empirical studies, the evidence is not as clear as clinicians like to believe, which might, in part, be due to methodological problems. Other pharmacological and biological treatment methods with lithium, neuroleptics, benzodiazepines, anti-epileptics and ECT are described as well.

Besides counselling and other psychotherapeutic approaches, psychopharmacological treatment and other biological treatment procedures (e.g. electroconvulsive therapy) are indicated for many suicidal patients. In people at risk of committing suicide, these interventions are usually aimed at actual prevention of suicide, mostly through sedative–anxiolytic or sleep-inducing approaches, or specific treatment of psychiatric disorders that are the underlying cause of suicidality. It is of great importance for patients in a critical life situation to be able to get rid of anxieties, depression, agitation, sleeplessness and other disturbing symptoms, even if these are not part of a full syndrome of a psychiatric disorder, but only subsyndromal. In this chapter, the psychopharmacological treatment of patients suffering from suicidality in defined psychiatric disorders is described.

The first part of this chapter describes pharmacological treatments of suicidality in the context of psychiatric disorders, and psychopharmacological approaches as used in clinical settings. The evidence for beneficial, as well as potentially harmful, effects of antidepressants on suicidality in depressive patients is also reviewed.

Depression is seen as the most frequent cause of suicidality and suicide. Although, the suicide lifetime risk in depressed patients is not much higher than, for example, in schizophrenic patients; depression is the most frequent reason for suicidality and suicide due to the high prevalence rate of depression. As to the differentiation between unipolar and bipolar depression, the suicide risk rate is more or less the same, i.e. about 10–15 per cent lifetime risk. Suicidal thoughts occur almost regularly in depression, especially in moderate or severe cases. Furthermore, a large number of patients think about suicidal acts, perform a suicide attempt or even die from suicide.

Antidepressants are the treatment of choice to reduce depressive symptoms of the depressive episode (Bauer et al. 2002, 2007), and also suicidal thoughts occurring in this context (Möller 2006a).

When selecting an antidepressant for severely suicidal depressive patients, traditionally, compounds with a sedative profile were favoured (e.g. amitriptyline or doxepin as representatives for the classic tricyclics, or mitrazepine as an example for a modern antidepressant [Möller and Volz 1996; Baghai et al. 2006]), although this view is not accepted by all experts. Drugs that increase drive, such as MAO inhibitors or desipramine, may increase the risk of suicide and should, therefore, be avoided (Möller 1992). Another aspect of drug selection is that the antidepressant should be safe in overdose, which is proven for most modern antidepressants, especially the selective serotonin reuptake inhibitors (SSRIs) (Wasserman 2006). If a tricyclic antidepressant (TCA) is chosen, the smallest package should be prescribed to avoid the risk of lethal intoxication in case of suicidal overdose. Most TCAs have a high risk of fatal outcome if dosages of 1000mg or more are taken. SSRIs are, nowadays, seen as the first-line treatment of depression, particularly under outpatient conditions, and especially with respect to tolerability and compliance (Möller 1992; Möller and Volz 1996). It should be remembered that SSRIs, as well as the selective serotonin–noradrenalin reuptake inhibitor venlafaxine (Baghai et al. 2006), have no sedative potential and, in some cases, even cause agitation.

The degree of sedation achieved by a sedative antidepressant in highly excited suicidal depressive patients is sometimes insufficient, so that it may be necessary to prescribe a benzodiazepine or a sedative neuroleptic (Möller 1999). The dose depends on the patient's condition and individual reaction. It should be chosen in a way that the inner restlessness and agitation wear off completely, or as far as possible, and significant sedation and promotion of nocturnal sleep are achieved. In the case of delusional depressions, highly potent neuroleptics (e.g. 5–10mg haloperidol orally or parenteral) are indicated in addition to antidepressant treatment. In cases of severe depression with extreme suicidality, electroconvulsive therapy (Fink 2005) should be considered, because of the rapid onset of action in comparison with antidepressants. Electroconvulsive therapy (ECT) is also an important option in patients who are refractory to antidepressant treatment (Möller 1994a).

However, we lack systematic knowledge on potential suicide preventive effects of this type of treatment, since hardly any adequately controlled treatment studies have been conducted on ECT with suicidal behaviour as their focus. A large Finnish national psychological autopsy study found that a remarkably low number of suicide cases had received ECT during the final months before suicide, thus suggesting that ECT may indeed have a suicide-preventive effect, (Isometsa et al. 1996). In a Swedish retrospective case–control study, there seemed to be a reduced risk of suicide in those patients who had received follow-up treatment with antidepressant medication after ECT (Brådvik and Berglund 2000).

Attention should be paid to two additional problem points when antidepressants are given to suicidal depressive patients. First, immediate antidepressant therapy is contraindicated in cases of intoxication with psychotropic substances (e.g. in an attempted suicide). In case of need, the fading period of intoxication should be bridged with sedating neuroleptics. Secondly, an increase in drive or normalization of reduced drive often occurs during antidepressant treatment prior to brightening of mood (so-called drive–mood dissociation). This may require temporary prescription or dose increase of a concomitant sedative medication until mood starts to brighten, in order to counteract the increased risk of acting on suicide impulses. This is of special importance with certain drugs, like the SSRIs, which are not sedative and, sometimes, even induce agitation or akathisia (Möller 1992; Möller 2006b). As a general rule, it should be considered that depressive patients treated with antidepressants should be observed carefully in the first days/weeks after treatment indication to assess and counteract as soon as possible negative changes in their degree of suicidality.

Unipolar and bipolar depressions are usually recurrent. Thus, in patients who have had two or more recurrent episodes, treatment is required to prevent relapse subsequent to acute and maintenance treatment. Antidepressants or lithium are candidates for preventing relapse in unipolar depression (Bauer et al. 2002, 2007). In bipolar depression (Grunze et al. 2002), lithium is generally the first choice; carbamazepine and valproate are the alternatives in special indications, such as resistance to lithium treatment or lithium intolerance. Recently, atypical antipsychotics have demonstrated relapse/recurrence preventive properties, but hitherto only in patients recovering from a manic episode. Of great interest is the increasingly confirmed result that prophylactic treatment with lithium reduces the well-known excess mortality of patients with unipolar or bipolar depression to within the normal range. This effect is apparently not only due to the reduction of depressive relapses and related suicidal behaviour, but also seems to be the consequence of a direct effect on suicidal behaviour itself (Thies-Flechtner et al. 1996; Müller-Oerlinghausen and Berghofer 1999; Goodwin et al. 2003; Fleischhacker et al. 2005).

Cipriani and co-workers' review and meta-analysis (2005) of 32 randomized trials of lithium versus other compounds (active or placebo) showed that lithium reduced the suicide mortality with approximately 60 per cent and the risk of suicide and deliberate self-harm combined by about 70 per cent. Lithium prophylaxis should, therefore, clearly be considered for patients with bipolar disorder who have displayed suicidal behaviour.

Until now, no differentiation was made with respect to the drug treatment of depressive episodes occurring during unipolar or bipolar affective disorder. In the last decade, great emphasis was placed on the fact that the treatment of bipolar depression should consider some special issues, especially the risk that antidepressants may induce a switch into mania. Therefore, some guidelines recommended avoiding antidepressants, and favour a monotherapy with lithium or anticonvulsants used as mood stabilizers. However, it has not been proven that these compounds have antidepressive efficacy comparable to that of the antidepressants (Möller and Grunze 2000). For this reason, antidepressants should still be regarded as the treatment of choice in bipolar depression (Grunze et al. 2002; Goodwin 2003; Möller et al. 2006a). SSRIs should be preferred due to their almost complete lack of risk for switching to mania. If the prescription of TCAs, which induce switching to mania in about 10 per cent of patients, is deemed clinically necessary, co-medication with a mood stabilizer is recommended to reduce the risk of switching to mania.

In mixed states, i.e. the coexistence of depression and manic symptoms (Balazs et al. 2006), as well as in patients with rapid cycling, antidepressants should be completely avoided; in such cases, treatment has to rely on lithium or other mood stabilizers only. Based on recently published data on olanzapine and quetiapine (Calabrese et al. 2005; Perlis et al. 2006; Perlis 2007), it appears that these, and possibly other atypical neuroleptics, will become an option for the treatment of patients suffering from a depressive episode in the frame of a bipolar affective disorder.

Schizophrenia has a virtually similar lifetime risk for suicide as unipolar or bipolar depression. The symptoms of schizophrenia can be easily treated with antipsychotics (Falkai et al. 2005). Second generation antipsychotics are increasingly in use in recent years, because of their lower liability to extra-pyramidal side effects, and a broader spectrum of efficacy (Möller 2000, 2002). Suicidality associated with a schizophrenic psychosis often requires medication in addition to the standard neuroleptic treatment of the schizophrenic symptoms, especially in cases of severe anxiety or excitation. Sedating neuroleptics or benzodiazepines are indicated in these conditions. If high doses of sedating neuroleptics are initially required to achieve adequate sedation, special attention must be paid to the risk of orthostatic hypotension.

A different approach is required for suicidality in schizophrenic patients who have depressive or negative symptoms. If depressive–apathetic symptoms with suicidality exist as part of a post-psychotic depression, or a deficit syndrome, pharmacotherapy should generally follow the guidelines for the treatment of these conditions. This means that treatment with antidepressants in the case of post-psychotic depression, and treatment with atypical neuroleptics, or SSRIs (or both) in the deficit syndrome, is necessary (Möller 2005b; Möller et al. 2006; Möller 2006a). If the suicidal symptoms are a side-effect of treatment with classical neuroleptics (pharmacogenic or akinetic depression), the neuroleptic dose should be reduced, if possible, or the patient should be switched to an atypical neuroleptic. An anti-parkinsonism drug, such as biperidon, is often advisable for some days to reduce the parkinsonian side-effects as soon as possible.

Atypical antipsychotics are the treatment of choice for long-term relapse prevention in schizophrenia, which is usually required subsequent to the acute episode, because they have no or a lower risk of inducing depression compared to the first generation antipsychotics, and may even have antidepressant effects (Möller 2005a, b). Atypical neuroleptics, thus, possibly reduce not only depression, but also related suicidality. Of special interest is that clozapine seems to have a special antisuicidal efficacy in the long-term treatment of schizophrenic patients (Meltzer and Okayli 1995; Meltzer et al. 2003). The study of Spivak et al. (2003)suggests that the reduction in suicidality following long-term clozapine treatment may be related to a reduction in impulsiveness and aggression.

Anxiety disorders and anxiety are often associated with the risk of suicidality. In addition to psychotherapeutic procedures, nearly all anxiety disorders and obsessive–compulsive disorders (OCD) are an indication for psychopharmacological treatment. Serotonergic antidepressants, especially SSRIs, are the treatment of choice, but also the dual selective reuptake inhibitor venlafaxine has demonstrated efficacy in some of these conditions (Bandelow et al. 2002). Administration of a benzodiazepine is often necessary for the acute control of panic situations. Antidepressants are also very often indicated in so-called neurotic disorders, depending on the type and severity of the symptoms. Examples include dysthymia (for which TCAs of the amitriptyline type, monoamine oxidase [MAO] inhibitors or SSRIs are used, for example), anxiety disorders (for which imipramine and SSRIs are used, for example) and OCD (for which clomipramine and SSRIs are used, for example). If suicidality occurs during such disorders, monotherapy with an antidepressant is often not sufficient to overcome the critical situation as quickly as possible. Short-term administration of benzodiazepines or sedative neuroleptics, along with the antidepressant, may be necessary. However, the application of a benzodiazepine should be restricted to a short period of days or a few weeks to avoid the risk of a low-dose dependency.

Personality disorders are frequently associated with chronic, repetitive suicidality. At special risk are histrionic and borderline patients. In general, the efficacy of psychopharmacological treatment of personality disorders is not well established (Kapfhammer and Hippius 1998; Cardish 2007; Herpertz et al. 2007). In borderline cases, the occasional risk of paradoxical reactions to benzodiazepines or TCAs, and possibly also to modern antidepressants like the SSRIs, should be taken into consideration (Möller 1994b). In most cases, only pharmacological treatment of the acute critical condition seems indicated. Benzodiazepines, antidepressants with a sedative–anxiolytic profile or low potency neuroleptics in small dosages, can be administered in this indication as a short-term intervention. It should be taken into account that these suggestions are mostly based on clinical experience, but not on clinical trials. Long-term treatment with benzodiazepines should be avoided due to the risk of abuse.

Over the last years, atypical neuroleptics have gained more widespread use for patients with BPD and seems to have promising effects on impulsivity and suicidal behaviour (Zanarini and Frankenburg 2001; Hilger et al. 2003), especially when they are used in combination with psychotherapeutic measures (Soler et al. 2005). Low-dose neuroleptics or atypical neuroleptics may also be necessary to use in the treatment of patients with BPD, in order to strengthen reality control or to reduce dissociative symptoms.

There are very few studies that have investigated whether a medium-term psychopharmacological approach might be useful in the prevention of further suicide attempts in patients with a history of repeated suicide attempts. The studies that have been performed have mostly involved patients suffering from comorbidity with personality disorders of the impulsive, histrionic and borderline type (Montgomery et al. 1992).

When suicidality results from abnormal reactions to psychosocial stress, psychopharmacological interventions are mainly aimed at sedation, anxiolysis, sleep induction, or suppression of disturbing vegetative symptoms.

Anxiolytic benzodiazepines, or in cases of predominant sleep disturbances, sleep-inducing benzodiazepines, or the modern non-benzodiazepine hypnotics, are generally the treatment of first choice in adjustment disorders. The selection of the specific compound and of the dose varies according to the individual case. The aim should be to induce not only sedation, but also affective–emotional distancing. Some doctors tend to be very restrictive in prescribing benzodiazepines, even under these conditions, because they are afraid of the risk of dependency. They prefer to use sedating antidepressants, such as doxepin, or low doses of sedating neuroleptics as surrogates. However, given the extraordinary good tolerability of benzodiazepines and the high compliance of patients with these drugs, the risk–benefit assessment should favour the benzodiazepines under these special conditions, especially given the fact that, in general, only short-term medication is needed. An inadequate psychopharmacological regime could induce a high risk of continuation of suicidality, and for this reason, under-treatment with benzodiazepines, which seems to become a general problem in patients with a need for benzodiazepine treatment (Möller 1999), should be avoided. In cases of longer-lasting depressive reactions, antidepressants should be considered. Modern antidepressants with better tolerability than the TCAs should preferably be chosen.

The psychopharmacological treatment of post-traumatic stress disorder is not yet well defined. Most experts recommend SSRIs, while benzodiazepines are not seen to be a treatment of choice (Asnis et al. 2004; Davidson 2004; Ursano et al. 2004).

Due to the role of depressive disorders, as the most frequent cause of suicidal behaviour, antidepressants have the most prominent place in psychopharmacological prevention of suicidal behaviour. Clinicians assume that antidepressants not only reduce depressive symptoms, but also the associated suicidality. This clinical experience is confirmed at least in terms of suicidal ideation by the results of controlled antidepressant studies, which show that if the depression subsides during treatment with antidepressants, the suicidal thoughts usually also diminish or disappear (Möller 2006a).

However, in the early publications on antidepressants, there are hardly any special studies on this topic. Much more interest in exploring this matter was shown later in the context of the question whether certain antidepressants reduce suicidal thoughts more quickly or effectively, particularly after the advent of the SSRIs.

A pooled analysis of all data from control group studies of the SSRI fluoxetine, involving a total of 1765 patients treated with fluoxetine, 569 with placebo and 731 with TCAs, found that suicidal ideation improved significantly more with fluoxetine than with placebo (72.0 per cent vs 54.8 per cent, p < 0.001), and was similar to the improvement with TCAs (72.5 per cent vs 69.8 per cent, p = 0.294) (Beasley et al. 1991). It is important to underline that, in terms of suicidal behaviour (suicide attempts and suicide), there is no relevant difference: the pooled incidence of suicidal acts was 0.3 per cent for fluoxetine, 0.2 per cent for placebo and 0.4 per cent for tricyclics. The slight numerical differences were not statistically significant. If only placebo-controlled fluoxetine studies were included in the pooled analysis, the rate in the fluoxetine and placebo groups was the same: 0.2 per cent (Beasley et al. 1991).

Similar results were also obtained in the pooled analysis of the results of a paroxetine study (Figure 54.1) (Lopez-Ibor 1993). The change in the Hamilton Depression Scale (HAM-D) suicidality item score over time showed that paroxetine and the active control were significantly superior to placebo in reducing suicidal thoughts from week 1 onward. In terms of frequency of attempted suicide and suicide, documented as adverse events, there were no statistically significant differences between the groups. The frequencies for suicides were as follows: 0.17 per cent for paroxetine, 0.26 per cent for active control and 0.36 per cent for placebo; the frequencies for attempted suicides were 1.3 per cent for paroxetine, 1.0 per cent for active control and 1.1 per cent for placebo.

Altogether, these findings provide some evidence that antidepressants are able to reduce suicidal thoughts in depressive patients. This effect is associated with the global antidepressive effect (Möller 2006a).

From a clinical perspective, one might hypothesize that the beneficial effect on suicidal ideation has consequences for the prevention of suicide attempts or even completed suicide. However, empirical data from randomized controlled studies, and even the pooled analyses of fluoxetine or paroxetine comparator trials, give no support to this hypothesis. Methodological limitations may not allow this question to be addressed adequately. The extremely low basal rate of suicide attempts, and especially completed suicide, is a limiting factor in short-term studies of antidepressants. Even meta-analytical approaches on huge datasets involving not only one experimental antidepressant but several, are apparently not able to overcome the respective statistical power problem of individual studies. Khan and colleagues (Khan et al. 2000, 2001, 2003) analysed several FDA databases on randomized, placebo- and/or active comparator-controlled trials on new antidepressants, mostly SSRIs. The analysis of this huge database did not find any significant differences between placebo, active comparator or investigational antidepressants in the rates of attempted or completed suicide. In a similar meta-analysis (Storosum et al. 2001), all randomized and placebo-controlled, double-blind, short- and long-term studies of an antidepressant that were part of a registration dossier submitted to the Dutch regulatory authority between 1983 and 1997 were reviewed for attempted suicide. In addition, all long-term, placebo-controlled antidepressant studies that were conducted in the last decade in patients with major depression were identified by a Medline search and assessed for attempted suicide. The analysis of this huge database was unable to demonstrate a significant difference in the risk of suicide attempts between active compounds and placebo. When interpreting the results of the long-term studies, it should be considered that even under these long-term conditions (the duration of most of the studies was one year), the base rate of suicide attempts was low, i.e. up to 0.2 per cent.

In contrast, two other huge meta-analyses (Fergusson et al. 2005; Gunnell et al. 2005) found an increased risk of suicide attempts for antidepressants, where in the latter study, the risk was only small and did not reach statistical significance. Thus, the overall findings from pooled analyses/meta-analyses of results of randomized, controlled, short- and long-term trials (mostly up to one year) do not support the hypothesis that antidepressants reduce attempted or completed suicide (Möller 2006a). This astonishing result, which appears to contradict general clinical experience, together with the findings from randomized controlled trials that antidepressants reduce suicidal thoughts, might be due to methodological pitfalls, such as a low base rate of the outcome criteria suicide attempts or suicide, and recruitment of a low-risk population. The result of the meta-analysis by Fergusson and colleagues (Fergusson et al. 2005) shows that, in contrast to the general expectations, there might be an increased risk of suicidal behaviour as a consequence of treatment with antidepressants, which requires further discussion (Möller 2006b).

Interesting data demonstrating the capacity of antidepressants to reduce suicidal behaviour was obtained in recent years from epidemiological studies (Möller 2006a). In view of the fact that it appears to be extremely difficult to prove the anti-suicidal effect of antidepressants in randomized, control group studies, such a naturalistic approach, seems to be one of the best ways to obtain at least some evidence. These studies are backed up by data from awareness and follow-up trials. However, naturalistic studies, on an ecological level, are always difficult to interpret due to several potential confounding factors, which require careful consideration.

The prescription rate of antidepressants has increased in several countries in the past decades, partly associated with the fact that modern antidepressants are better tolerated and, therefore, easier to handle in the everyday routine care situation, especially in primary care. This increased prescription of antidepressants offers the possibility of a quasi-experiment, in which the suicide rates at the time of a lower and higher prescription rate can be compared.

For example, Isacsson analysed such data in a study on suicide rates in Sweden and other Scandinavian countries (Figure 54.2) (Isacsson 2000). He took into account relevant confounding factors, which might explain the change in suicide rates, like unemployment rates and alcohol consumption. However, this was not performed using complex statistical procedures, but only by looking at the development of each of these variables over time. The suicide rate in Sweden decreased by 19 per cent in parallel with the increased use of antidepressants, from 23.3 suicides per 100,000 inhabitants in 1991 to 18.8 in 1996 (rho = −0.90, p < 0.05). Considering subgroups in Sweden during 1990–1996, there were no demographic groups with regard to age, gender or county in which the suicide rate decreased in the absence of an increased use of antidepressants. In women under 30 and over 75 years of age, however, and in four of the 23 counties, suicide rates remained unchanged despite an increased use of antidepressants. Inverse correlations between the use of antidepressants and suicide rates were also seen in the three other Scandinavian countries, Denmark (rho = −0.94, p < 0.01), Norway (rho = −0.87, p < 0.05) and Finland (rho = −1.00, p < 0.01), during 1990–1996. There was no consistent correlation in Sweden (1978–1996), between suicide rates and alcohol consumption, or between suicide rates and unemployment rates (Isacsson 2000). In this epidemiological study, it appears that the increased use of antidepressants was one of the contributing factors to the decrease in the suicide rate.

Grunebaum and colleagues (Grunebaum et al. 2004) presented the results of a methodologically sound analysis of the US-American data for the years 1985 to 1999 that took into account unemployment and alcohol consumption as confounding factors in a multivariate approach. The relationships between the suicide, antidepressant prescription, unemployment and alcoholic beverage consumption rates were studied using generalized linear models. Suicide rates by antidepressant overdose were compared in SSRIs and TCAs. From 1985 to 1999, the suicide rate fell 13.5 per cent, with a greater decline among women, and antidepressant prescription rates increased over fourfold, with the increase mostly due to SSRIs. Prescription rates for SSRIs, and other second-generation antidepressants, were both inversely associated with suicide rates (p = 0.03 and p = 0.02, respectively). In a multivariable analysis adjusting for unemployment and alcoholic beverage consumption rates, SSRI antidepressant prescription rates remained inversely associated with the national suicide rate (p = 0.03). The authors came to the conclusion that the decline in the national suicide rate (1985–1999) appears to be associated with greater use of non-tricyclic antidepressants. A similar study on suicide data from the USA performed by Gibbons and colleagues (Gibbons et al. 2005) obtained similar, but somewhat more differentiated results.

Other epidemiological studies confirmed the positive results (Rihmer 2001; Hall et al. 2003; Kelly et al. 2003; Rihmer 2004). In order to give a balanced overview, it should be mentioned that two studies were unable to support the findings of an association between an increased prescription rate of antidepressants and a decreased suicide rate (Barbui et al. 1999; Helgason et al. 2004).

These studies results on an epidemiological level show that it is evident that an increased utilization of antidepressants, especially SSRIs, was accompanied by a relevant decline of national suicide rates in several countries (Möller 2006a), particularly in those where the suicide rates were previously very high. The results of complex and sophisticated statistical analyses show that this relationship cannot only be explained by potential confounding variables. It can be considered to be a very robust epidemiological finding, due to the fact that it could be replicated in several countries under different psychosocial and care conditions (Möller 2006a). Apparently, in terms of suicide rates, certain subgroups of the population are influenced to different degrees by the prescription of antidepressants. The US Food and Drug Administration (FDA) analyses show a pattern of increasing benefits and decreasing risk of suicidal behaviour in treatment with antidepressant in all age groups, with the exception of those under the age of 18 and young adults aged 18–24 years (see Chapter 91 by David Brent).

The most common psychiatric illness seen to be associated with suicide is a depressive disorder (Möller 2003). Isacsson and colleagues (Isacsson et al. 1996), for example, found that the risk for suicide among depressed patients who were treated with antidepressants in Sweden was 141 per 100,000 person years and, among the untreated, 259 per 100,000 person years (i.e. 1.8 times higher among the untreated).

Although, a lot of patients seek professional help in the month before committing suicide (Isacsson et al. 1992), post-mortem studies show that most patients are untreated at the time of death (Isometsa et al. 1994; Isacsson et al. 1997; Oquendo et al. 1999). The huge proportion of under-diagnosed and undertreated depressive patients is also known from several studies on the care of depressive patients, e.g. the DEPRES study (Lepine et al. 1997; Tylee et al. 1999a, b; Angst et al. 2002). Thus, it seems reasonable to suggest that the important strategy for lowering suicide rates should be to identify all individuals with depressive disorders and to intervene effectively.

Awareness and education campaigns seem to be an appropriate approach in achieving this goal (Mann et al. 2005). A milestone in this respect is the so-called Gotland study. In 1983–1984, the Swedish Committee for the Prevention and Treatment of Depression offered an educational programme on the diagnosis and treatment of depressive disorders to all general practitioners on the island of Gotland. The programme was carefully evaluated: 1982 was used as the baseline, and the main evaluation was carried out in 1985 (Rutz et al. 1992). After the educational programmes, the frequency of sick leave for depressive disorders decreased, and the frequency of inpatient care for depressive disorders decreased to 30 per cent of that at the baseline, the prescription of antidepressants increased, but prescription of major tranquillizers, sedatives and hypnotics decreased. The frequency of suicide on the island among females decreased significantly.

A programme called the Defeat Depression Campaign was carried out in Great Britain for five years from 1992 to 1996. It was aimed at enhancing public awareness of, and attitudes toward, depressive disorders by providing professional education for general practitioners and reducing the suicide rate (Paykel et al. 1997). The campaign was evaluated through three representative surveys of public attitudes (1991, 1995, 1997) (Paykel 2001). The surveys showed a progressive increase in the general population's knowledge about the biological causes of depressive disorders. However, the campaign did not result in a sustained improvement of patient care (Rix et al. 1999), or in a change of entrenched public attitudes, for example, the negative opinion about treatment with antidepressants (Paykel et al. 1998). The prescription rate of TCAs and SSRIs increased over the course of the campaign (Paykel 2001). A basic problem of the study is that there was no control region, so it cannot be elucidated whether the measured effects were related to the campaign or possible changes in the health care system.

The Nuremberg Alliance against Depression programme, which was carried out in the German city of Nuremberg, is another, even more complex, study that combined an educational programme addressed at general practitioners with a public awareness campaign for depression (Hegerl et al. 2003; Henkel et al. 2003; Althaus et al. 2005; Hegerl et al. 2008). It confirmed the principal results of the Gotland study, while using a more sophisticated evaluation methodology, for example, involvement of a control region in the evaluation.

As is always the case in such quasi-experimental, but complex intervention programmes, it is difficult to decide which factors are responsible for the achieved effects. Besides the improved diagnosis and treatment of depression, changes in the prescription rate of antidepressants are probably also relevant (Pfeiffer-Gerschel 2007).

Altogether, there seems to be reasonable evidence from different research approaches that antidepressants are able to reduce suicidal ideation, and also suicide in depressive patients. While the evidence for the beneficial effect on suicidal ideation comes from randomized, control group studies, some of which used a placebo arm, the evidence for the prophylactic effect on suicide was primarily obtained from well-designed epidemiological studies.

Finally, the question whether antidepressants can induce or aggravate suicidal ideation, or even stimulate suicidal behaviour, should be briefly addressed in this paper, because it has attracted so much attention in recent years, especially in the field of child and adolescent psychiatry. A review of the evidence concerning children and young people is given in this book (see Chapter 91).

A comprehensive review (Möller 2006b; Tandon et al. 2008) came to the following conclusions in this regard:

In everyday clinical practice, the discussion about the possible risks of the SSRIs or antidepressants, in general, should not result in clinicians forgetting the benefits of these drugs. The symptoms of depression require an effective drug treatment accompanied by the chance to reduce suicidal thoughts. Of course, particularly at the start of treatment, patients are often very labile; and in single cases, antidepressants, depending on their specific pharmacological and pharmacodynamic characteristics and in interaction with special characteristics of the patient, such as personality traits, comorbidity etc., can potentially induce or enhance suicidal thoughts, or even reduce the threshold potential for suicide attempts. It is a matter of good clinical practice to monitor the patient carefully, especially at the start of drug treatment, and try to avoid any kind of risk. If agitation, sleep disturbances or other drug side effects that may potentially induce or enhance suicidality occur, a sedating or sleep-inducing co-medication should be administered. It is also of greatest importance to offer the patient a substantial supportive psychotherapy. Finally, it should not be forgotten that depressive symptoms and suicidal thoughts can fluctuate during the day or over longer time periods. It is often difficult to follow this carefully enough on an outpatient basis, so that inpatient treatment might be a better option for patients at risk (Möller 2006b).

Going beyond the antidepressants, the important role of another drug, lithium, in the field of suicide prevention should be mentioned. Several analyses of lithium prevention studies show that the excess mortality, usually shown by depressive patients in comparison to the general population, can be reduced to the normal level by lithium relapse prophylaxis. This effect of lithium could not only be explained by its relapse-prophylactic effect, but was interpreted as being a specific influence on suicidality, potentially by the serotonergic effects of lithium (Müller-Oerlinghausen 1989; Coppen et al. 1991; Tondo et al. 2001; Goodwin et al. 2003; Cipriani et al. 2005). The finding that a raised lithium concentration in drinking water correlates with a lower suicide rate is also of interest (Schrauzer and Shrestha 1990). Lithium relapse prevention in unipolar or bipolar patients seems therefore meaningful whenever there is an indication for lithium long-term treatment.

Psychiatric disorders can cause suicidality. Given the high prevalence and lifetime risk of depressive disorders, depression is one of the major causes of suicidal behaviour. Adequate psychopharmacological treatment of depression and other psychiatric disorders associated with suicidality is recommended as a meaningful strategy to reduce suicidal thoughts and suicidal behaviour. Depending on the individual disorder and the specific conditions, this includes the administration of antidepressants, antipsychotics, benzodiazepines and hypnotics. The psychopharmacological intervention should aim to have a positive effect on suicidality as soon as possible. In critical situations, co-medication is often clinically indicated, e.g. the combination of an antidepressant with a benzodiazepine.

The findings of randomized, control group studies in acute depressive patients supply good evidence that antidepressants are able to reduce suicidal thoughts in depressive patients. However, data from randomized, control group studies in acute depressive patients give no support to the hypothesis that antidepressants can reduce suicide attempts or suicide. The extremely low base rate of suicidal behaviour in these studies is, apparently, a principal methodological problem, which makes it almost impossible to demonstrate, under such conditions, a beneficial effect of antidepressants on suicidal behaviour. Even meta-analyses of huge datasets from randomized, controlled trials seem unable to overcome this problem. Thus, complementary methodological approaches have to be applied.

Over the past year, there have been intensive discussions about possible negative effects of antidepressants on suicidality. Although there is only weak evidence for such effects when treating individual patients with antidepressants, the potential, but rare risk, of inducing suicidality should be considered carefully. Optimal clinical management can avoid possible harmful consequences of treatment with antidepressants.