7
Medical and Psychotherapeutic Interventions

Almost half of the individuals who complete suicide in the United States are diagnosed with a mental disorder and are under treatment by a mental health professional (Conwell et al., 1996; Fawcett et al., 1991; Harris and Barraclough, 1997; Isometsa et al., 1994; Robins et al., 1959). To be able to prevent suicide through treatment and therapy, it is necessary to know when the individual is in immediate danger of dying by suicide. However, existing assessment instruments may help in identifying who is at risk, but do indicate when they will be at risk. Further, since certain life events can precipitate suicide in some but not all patients, their predictive value is poor. Many at-risk patients receive medication for mental disorders. But while these medications often reduce the symptoms of these disorders, the effectiveness of such medications to decrease the risk of suicide is unknown. Medications are best delivered in the context of a therapeutic relationship featuring an ongoing and appropriate psychotherapy or counseling, conscientious follow-up, and an overall flexible treatment plan that considers the socio-cultural context of the patient. This chapter addresses issues of assessment, reviews current knowledge about the effectiveness of medications for suicidality, and describes the impact of hospitalization and psychotherapy on suicidality.

ASSESSMENT

Suicide risk is difficult to assess. Individuals making serious suicide attempts may knowingly withhold their intentions (e.g., Apter et al., 2001;



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Reducing Suicide: A National Imperative 7 Medical and Psychotherapeutic Interventions Almost half of the individuals who complete suicide in the United States are diagnosed with a mental disorder and are under treatment by a mental health professional (Conwell et al., 1996; Fawcett et al., 1991; Harris and Barraclough, 1997; Isometsa et al., 1994; Robins et al., 1959). To be able to prevent suicide through treatment and therapy, it is necessary to know when the individual is in immediate danger of dying by suicide. However, existing assessment instruments may help in identifying who is at risk, but do indicate when they will be at risk. Further, since certain life events can precipitate suicide in some but not all patients, their predictive value is poor. Many at-risk patients receive medication for mental disorders. But while these medications often reduce the symptoms of these disorders, the effectiveness of such medications to decrease the risk of suicide is unknown. Medications are best delivered in the context of a therapeutic relationship featuring an ongoing and appropriate psychotherapy or counseling, conscientious follow-up, and an overall flexible treatment plan that considers the socio-cultural context of the patient. This chapter addresses issues of assessment, reviews current knowledge about the effectiveness of medications for suicidality, and describes the impact of hospitalization and psychotherapy on suicidality. ASSESSMENT Suicide risk is difficult to assess. Individuals making serious suicide attempts may knowingly withhold their intentions (e.g., Apter et al., 2001;

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Reducing Suicide: A National Imperative Morrison and Downey, 2000; Negron et al., 1997). No psychological test, clinical technique, or biological marker is sufficiently sensitive and specific to accurately assess short-term prediction of suicide in an individual (Goldstein et al., 1991). A prospective study (Pokorny, 1983) of 4800 consecutive patients at a Veterans Administration hospital used 21 known suicide risk factors to identify 803 patients with increased risk of suicide. Thirty of these identified patients completed suicide during a 5-year follow-up period. But an additional 37 patients than had not been assessed as at-risk also completed suicide. Even an optimal measure with the unrealistically low rate of false-positives and false-negatives (1 percent) would only correctly assess 20 percent of those who complete suicide (MacKinnon and Farberow, 1976). Assessment instruments can be useful tools but are not a substitute for clinical judgement. Nevertheless, assessment is an important component of psychopharmacological and psychotherapeutic interventions. Assessment Instruments Whether using a standardized psychological test or interview only, it is important to assess for suicidal symptoms, symptoms of the known risk factors for suicide, and current abilities to cope with acute or chronic stress (Bech et al., 2001). Assessment instruments fall into four broad categories: (1) detection instruments, (2) risk assessment instruments, (3) assessment of clinical characteristics of suicidal behavior, and (4) a miscellaneous category (e.g., compilations, assessment of attitudes around suicide, projective psychological tests1). Assessment tools for adults and youths have been extensively reviewed by Brown (2000) and Goldston (2000), respectively. One of the most widely used and best-evaluated measures is the Scale for Suicide Ideation (SSI) (Beck et al., 1979). It is a 19-item scale, available as interview, self-report, or computer-administered. Only if a person endorses an item indicating intent to complete suicide, is the rest of the scale administered. It has been standardized on both inpatient and outpatient clinical samples. It has also been used in emergency rooms, primary care settings, jails, and in college student samples. A prospective study with almost 7000 patients and an approximately 20-year follow-up with psychiatric outpatients used standardized, structured interviews and standardized assessment measures (Brown et al., 2000). These data were 1   Projective psychological tests use abstract, or non-definitive test stimuli allowing the test subject to project their psychological makeup onto the material.

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Reducing Suicide: A National Imperative matched to the National Death Index, and death certificates were obtained for those who had died. Through this process, 49 suicide cases were identified. The average length of follow-up was 10 years, and the average length of time to death was approximately 4.3 years from the baseline interview. Patients who scored above 3 on the SSI were about 6.5 times more likely to complete suicide than patients who scored below this cut-off. Other scales that have been shown to have some predictive validity include the Beck Hopelessness Scale, Beck Depression Inventory, Beck Anxiety Scale, and the Hamilton Rating Scale for Depression. Measurements of personal contentment, such as Linehan’s (1983) Reasons for Living Inventory and Koivumaa-Honkanen and colleagues’ (2001) simple life satisfaction measure, also seem to have value in some populations. All of the instruments have their strengths as well as their weaknesses, but there may be no single “best” instrument for all purposes. The choice of instruments depends on the needs of the clinician or researcher, the intended use of the instruments, and an assessment of how an instrument compares to other similar instruments in meeting diagnostic needs. Furthermore, the age, gender, and culture of the suicidal individual must also be considered in choosing assessment scales. Some measures of psychopathology and suicide risk may not be as accurate or appropriate for specific populations, since risk and protective profiles differ across ethnicity, gender, and age. Cognitive measures of mental disorders, for example, may not be as sensitive for ethnic groups that experience psychopathology in more somatic than in cognitive terms (Marsella et al., 1975; Marsella and Yamada, 2000), and culture and developmental stage (e.g., single adolescent vs. adult parent) influence such things as reasons for living (see Chan, 1995; Linehan et al., 1983; Osman et al., 1998). Confounding Factors Variations in Purpose Assessment tools differ; there are detection instruments, risk assessment instruments, and instruments for assessing clinical characteristics of suicidal behavior. Each of these groups of instruments is useful for answering certain types of questions, but the use of the wrong instrument may yield insufficient or even misleading information. A risk assessment instrument will not provide information about whether someone is currently suicidal (an issue of detection). A person may score “low” on a risk assessment instrument assessing a particular domain (e.g., hopelessness) while still experiencing suicidal ideation or even having made a recent attempt (Goldston, 2000).

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Reducing Suicide: A National Imperative Incomplete Use Further confounding the use of assessment tools is their misuse. At times, researchers have used one or two items from an assessment scale, when the tools have only been validated in their full form. Studies frequently use just a single item from the Hamilton Depression Scale, a practice which results in a decreased sensitivity of the assessment tool. Complete, standardized suicide assessment measurements are most appropriate in clinical trials. Population Specificity Instruments may not have the same predictive utility when used in populations other than those in which they were developed (Meehl and Rosen, 1955). The base rate of risk factors may vary significantly across different populations, so that the same level of a risk factor may have significant predictive utility in some groups, but not others. In addition to base rate differences, risk factors may vary in meaning, salience, and/or presence across groups. The prevalence of risk factors for suicidal behaviors differs in different samples or population groups, just as the base rates of suicidal ideation and suicide attempts differ. Moreover, some instruments may be more appropriate than others for certain age groups, and some instruments may be more “culturally sensitive” than others. For these and other reasons, an instrument that has been demonstrated to be of use in one population may not be as useful with other groups. Instruments developed with school-based or community samples may not have the same predictive utility in “high-risk” or clinically ascertained samples, and vice versa. Risk factors in a community may not be useful as a predictor of suicidal behavior in higher risk populations. First-time suicide attempters may differ from those who attempt more than once, and predicting first and later attempts may involve different risk factors. Goldston’s team (2001) found that hopelessness was a strong predictor of future suicide attempts following hospitalization among adolescents who previously had made at least a single suicide attempt, but hopelessness was not a significant predictor in those without a history of suicide attempt(s). Distal vs. Proximal Factors The relationship between vulnerability factors assessed with risk instruments (distal risk factors) and precipitating stresses (proximal risk factors) needs to be better understood. Using instruments focused on identifying groups based on various risk factors may tell us who is at risk,

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Reducing Suicide: A National Imperative but not when they are at risk. Specific life events may precipitate or provide the occasion for suicidal behavior, but they do not tell us who is likely to make those attempts. The course or persistence of vulnerability factors over time and an individual’s reactions to life events and stressors are important influences. To accurately predict suicidal behavior, a better understanding of the interplay between vulnerability factors and stresses is needed. PSYCHOACTIVE MEDICATIONS Since 90 percent of suicide occurs in people with mental disorders, it is thought that treating the underlying disorder could reduce suicide risk. For some medications there is evidence that the effects on suicidality may be independent from the effects on the mental disorder. This section reviews the evidence that medications used to treat mental disorders can influence the risk of suicide. Mood Stabilizers Mood stabilizers are used to treat bipolar illness. These drugs fall into two major classes. The first is lithium, a naturally occurring salt, which is effective in reducing the manic and depressive symptoms. Another group of medications proven effective for bipolar disorder is the anticonvulsants (e.g., carbamazepine and valproic acid). Lithium Evidence suggests that lithium treatment of bipolar disorder significantly reduces suicide rates (Baldessarini et al., 1999). In fact, lithium may have specific anti-suicide effects for people with this disorder since these effects may be separate from its antidepressant and antimanic effects. A prospective, randomized controlled clinical trial (Thies-Flechtner et al., 1996) in patients with bipolar illness found that lithium carbonate significantly reduced suicidal acts per patient, relative to patient years. A series of reviews and a meta-analysis of the effect of lithium on suicidality by Tondo and colleagues (Tondo et al., 1997; 1998; 2001) supported the finding that lithium reduced the rate of both suicides and suicide attempts in bipolar patients. The meta-analysis of 12 studies on lithium reported that the risk ratio in favor of a therapeutic lithium effect on suicide is 8.85 (confidence interval=4.14-19.1) (Tondo et al., 2001). This estimate, if correct, would make lithium the most potent therapeutic agent so far identified. However, the protective effects of lithium are not consistent across studies (see Bowden, 2000; Brodersen et al., 2000), and some method-

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Reducing Suicide: A National Imperative ological concerns have been raised (Bowden et al., 2000; Calabrese et al., 2001a; Goodwin, 1999). Some also caution that although the data is mostly positive, the anti-suicidal effect of lithium may not be as strong as originally thought (Bowden et al., 2000). One of the confounding issues in these studies is the time course of psychopharmacological treatment. Decreased rates of suicide are most pronounced when lithium has been used for a minimum of 2 years (Baldessarini and Tondo, 1999). Rates were reduced only while the patients took lithium; following discontinuation of lithium, the rates began to rise to levels similar to those seen prior to the commencement of lithium. Rapid discontinuation of lithium may lead to a more dramatic increase in rates of suicidal behavior as compared to more gradual discontinuation. Early studies, because of their abrupt discontinuation of lithium, may have increased placebo relapse figures (Bowden et al., 2000). Tondo, Baldessarini and colleagues (Baldessarini and Tondo, 1999; Tondo and Baldessarini, 2000; Baldessarini et al., 1999; Tondo et al., 1997) noted that the latency from onset of bipolar disorder to lithium maintenance in their patients averaged 8.3 years, but that half of the suicidal acts had occurred in the first 7.5 years. Thus, it may be of crucial importance to commence lithium treatment as early as possible in the course of bipolar disorder for patients thought to be at risk for suicidal behavior. It is noteworthy that lithium and clozapine (see below) are both effective in reducing suicidal behavior and both require regular clinic visits and blood tests. This suggests a benefit from regular clinic monitoring. Nonadherence with medication, particularly lithium, is a critical issue for individuals with bipolar disorder and one of the primary reasons for poor treatment response (Goodwin and Jamison, 1990). Since lithium treatment is associated with an almost 8-fold decreased suicide rate (Tondo and Baldessarini, 2000), this has a serious impact on suicide risk. Research has shown that almost one-half of patients with bipolar disorder are non-adherent to lithium treatment at some point in their lives, and one-third are non-adherent two or more times (Jamison and Akiskal, 1983; Jamison et al., 1979). Younger males within the first year of lithium treatment and those patients who have elevated moods and a history of euphoric manias, especially those who complain about missing the “highs” of their illness, are more likely to be nonadherent (Goodwin and Jamison, 1990). Many people stop taking their medication after being released from the hospital, one of the factors causing significantly increased risk of suicide during this period (see below). Furthermore, clinical research with bipolar populations is very difficult due to poor treatment adherence (Goodwin and Jamison, 1990; Goodwin, 1999; Jamison and Akiskal, 1983; Jamison et al., 1979), and the poor adherence rate makes interpreting results more difficult and the conclusions less powerful in many studies.

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Reducing Suicide: A National Imperative Important questions regarding lithium still remain. Greil and colleagues (1996; 1997a; 1997b), in a series of randomized controlled studies with treatment periods of 2.5 years, found that the prophylactic efficacy of lithium on suicidality varied according to the underlying mental disorder. Carbamazepine was more effective than lithium in reducing suicidal behavior in schizoaffective disorder, especially in subgroups with depressive or schizophrenia-like features; in bipolar types it was not superior (Greil et al., 1997a). For unipolar depressed patients, lithium was found to be superior to amitriptyline (Greil et al., 1996), and in bipolar disorder patients, lithium was judged to be superior to carbamazepine (Greil et al., 1997b). Several studies also suggest that bipolar patients with rapid cycling or mixed states are difficult to treat effectively and do not seem to respond as well to lithium (Bowden et al., 2000; Calabrese et al., 2001b; Montgomery et al., 2000). Comorbidities, especially with substance use disorder, also interfere with treatment outcome (Macqueen and Young, 2001; Vestergaard et al., 1998), though comorbidity appears to moderate outcomes via treatment adherence (Calabrese et al., 2001b). The mechanism of action of lithium is unknown. It has been hypothesized that it exerts antisuicidal effects on aggressive impulsive traits via the serotonergic system or otherwise. Importantly, lithium appears to have a direct effect on suicidal behavior, not simply by reducing the suicidality caused by depressive relapses (Möller, 2001). Anticonvulsants The other class of mood stabilizers found to reduce symptoms of bipolar disorder are the anti-convulsants, such as carbamazepine, divalproex, and valproic acid. These medications are recommended for bipolar patients when lithium is not an option, whether due to lithium intolerance or resistance to lithium treatment (Möller, 2001). Valproate is the most commonly prescribed mood stabilizer in the United States, overtaking lithium. However the data are very limited on the efficacy of anticonvulsants to reduce suicidal behavior; only one randomized controlled study was identified in a recent review (Goodwin and Ghaemi, 2000). Thies-Flechtner et al. (1996) conducted a 2.5 year prospective study on 175 inpatients with bipolar disorder. These patients were treated either with carbamazine or with lithium. Of the 6 patients who committed suicide, 4 were taking carbamazine. None were taking lithium at time of death, but one had discontinued lithium. All of the suicide attempts occurred in patients who were taking carbamazine. These data demonstrated a statistically significant benefit of lithium over carbamazine in the prevention of suicide. Because of the frequency with which anticonvulsants are prescribed for bipolar disorder, it is exceptionally

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Reducing Suicide: A National Imperative important to evaluate their effectiveness compared to lithium for prevention of suicide. Anti-Psychotic Medications Anti-psychotic medications, including neuroleptics, may also be effective in the reduction of both suicidal behavior and the overall suicide rate when suicidality is seen as a feature of psychosis in schizophrenia. Particularly compelling evidence exists for the atypical anti-psychotic, clozapine. Meltzer (1999) found that the mortality rate from suicide was reduced by 80 to 85 percent of the expected rate for schizophrenic patients in a population of treatment-resistant schizophrenic patients treated with clozapine after adjusting for the duration of treatment. Recently, Meltzer and colleagues (2001) reported that in a multi-centered, randomized clinical trial of 980 patients with schizophrenia or schizoaffective disorder, treatment with clozapine when compared to treatment with olanzapine resulted in significantly fewer suicide attempts and a reduced need for additional medications to control suicidality. Meltzer and Okayli (1995) reported that clozapine in neuroleptic-resistant psychotic patients, when given as continuation or maintenance pharmacotherapy, was associated with markedly less suicidality. They reported that the number of serious suicide attempts decreased significantly and that this decrease was associated with a reduction in depression and hopelessness. Interestingly, they stated that the beneficial effect occurred independently of the response to the psychosis, so it appears to be more attributable to the effect on depression and hopelessness. Both treatment-responsive and treatment-resistant patients were included, but similar results were obtained in the two groups for both prior suicidal behavior and suicidal behavior on treatment. The suicide attempt rate fell from 25 percent prior to treatment to 3.4 percent after clozapine treatment. The lethality of the suicide attempts was also significantly reduced after clozapine treatment. Walker and colleagues (1997) reported on data from a national registry of clozapine recipients involving 67,072 current and former clozapine users, linking the data to the National Death Index and the Social Security Administration Death Master Files. They identified 396 deaths in 85,399 person-years for patients ages 10–54 years. Mortality was lower during current clozapine use than during periods of nonuse. The mortality from suicide decreased in current clozapine users by comparison with past users. The investigators confirmed that the principal reason for the reduction in deaths was a decrease in the suicide rate. Using the Texas Department of Mental Health and Mental Retardation database, Reid’s research

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Reducing Suicide: A National Imperative team (1998) found that the annual suicide rate for 30,000 patients with schizophrenia and schizoaffective disorders was 63.1 per 100,000 patients (between 1993 and 1995), approximately five times higher than in the general population. In contrast, only one suicide occurred in 6 years among patients treated with clozapine who were of similar diagnosis, age, and sex (a yearly rate of about 12.7 per 100,000 patients). Similarly, the suicide rate was found to be 15.7 per 100,000 patients per year in all United States patients treated with clozapine based on the clozapine national registry system maintained by Novartis Pharmaceutical Corporation, the United States manufacturer of clozapine. Similar analyses with other novel antipsychotic medications have been initiated, and preliminary results suggest that they may also have some beneficial effect in reducing suicide rates. Antidepressant Medications A number of investigators worldwide have recently reviewed outcomes across large populations showing that a decrease in suicides correlates with the increase of antidepressant use in various European countries (Isacsson et al., 1996; Markowitz, 2001; Ohberg et al., 1998; Rich, 1999; Rihmer et al., 1998) and that suicidal behavior correlates with the inadequate prescription of antidepressants (Henriksson et al., 2001; Oquendo et al., 1999). Such population-based changes in the suicide rate may be due to numerous causes in addition to the increase in antidepressant prescriptions, but these findings suggest a benefit from receiving antidepressants which may be related to appropriate treatment of the underlying depression. Psychological autopsy studies suggest that the rate of adequate treatment with antidepressants of depressed suicide victims is about 6–14 percent, and toxicological analyses indicate the presence of antidepressants and other prescription psychotropics in about 8–17 percent of suicides, with the frequency in men being about half that of women, and in Blacks and Hispanics being half that of Caucasians (Blazer et al., 2000; Isacsson et al., 1999; Marzuk et al., 1995; Rich and Isacsson, 1997). In general, surveys of university teaching hospitals indicate that most depressed outpatients, even in such academic centers, are either not treated or are under-treated with antidepressant medications (Keller et al., 1986; Oquendo et al., 1999). Oquendo and colleagues (1999) showed that this was just as frequent a problem for those depressed patients with a history of suicidal behavior as for those without. A variation on the epidemiological studies is the examination of the benefits of an educational intervention. Gotland, an island province of Sweden with a population of 58,000, is a single epidemiological catch-

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Reducing Suicide: A National Imperative ment area and most treatment is provided by general practitioners (GPs). In a series of papers since 1989, Rutz, Rihmer, and colleagues (Rihmer et al., 1995; Rutz, 2001; Rutz et al., 1989a; Rutz et al., 1989b) reported that educating the Gotland GPs about depression recognition increased the use of antidepressants and lowered suicide rates by 60 percent (see also Chapter 8). SSRIs Serotonin reuptake inhibitors (SSRIs) are used to treat depressive symptoms in the affective disorders as well as for symptom relief for those who have other diagnoses, or do not meet the criteria for the major affective disorders. SSRIs have gained great popularity in recent years, with the number of prescriptions increasing both in the United States and in other western nations (Isacsson, 2000; Lawrenson et al., 2000; Sclar et al., 1998). Although the SSRIs reduce depressive symptoms, their potency in reducing suicide is uncertain. Verkes et al. (1998) found that patients with personality disorders and brief depression, but not major depression, had fewer suicide attempts when treated with paroxetine as compared with placebo. On the other hand, most studies failed to find statistically significant differences in suicide or suicidal behavior with SSRI treatments. Leon et al. (1999) followed 185 patients treated with fluoxetine (from among 643 patients as part of the NIMH Collaborative Depression Study). Using a mixed effects survival analysis, they found a decreased risk of suicide attempts and completions in the fluoxetine group, but this decrease did not achieve statistical significance, perhaps because the patients given fluoxetine were more severely ill than the comparison group before treatment. On the other hand, three meta-analyses failed to show effects of the SSRIs on suicide. Two (Khan et al., 2001; Khan et al., 2000) assessed FDA trials for efficacy and found that the major SSRI antidepressants were not significantly different than placebo with respect to suicides. Another meta-analysis of 17 clinical trials (Beasley et al., 1991) indicated that fluoxetine may reduce suicidal ideation but was not significantly different from either placebo or the tricyclic antidepressants in reducing suicides or attempts. Several factors may enter into the interpretation of these results. Hirschfeld (2000) pointed out that these studies were time-limited. In addition, they mostly attempted to screen out those at risk for suicide. In most of the clinical studies, the base rate of suicide attempts was too low to determine effectively whether the antidepressant medications reduced the number of suicide attempts or suicides in comparison with placebo (Khan et al., 2001; Khan et al., 2000; Letizia et al., 1996; Montgomery et al., 1994; Tollefson et al., 1993). To a large extent, the low base rate of suicidal

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Reducing Suicide: A National Imperative acts in most studies was a consequence of the exclusion of suicidal patients for safety reasons (see Chapter 10). Some investigators (Khan et al., 2001; Khan et al., 2000) also note that the increased contact with mental health professionals for both treatment and placebo groups confounds the observed relationships, and could possibly represent a kind of treatment in itself. As mentioned earlier, however, increasing prescription rates for antidepressants, in particular SSRIs, has correlated with declines in suicide rates observed in a number of countries including Sweden, Finland, Hungary, and the United States (Isacsson, 2000; Ohberg et al., 1998; Rich and Isacsson, 1997; Rihmer et al., 2001). With access to national health data, it was found that with a doubling of the number of SSRI prescriptions, the suicide rate was reduced by 25 percent in Sweden (Isacsson et al., 1992). A similar result was reported in Italy, but the effect was confined almost entirely to females (Barbui et al., 1999). Though these correlations do not determine causality, they suggest the potential for antidepressants, particularly SSRIs, to reduce suicide rates. This is further supported by the findings of psychological autopsies and toxicological analyses that frequently have found that suicide victims with a mood disorder were taking inadequate therapeutic amounts of antidepressants (Blazer et al., 2000; Isacsson et al., 1994; Isacsson et al., 1992; 1997; Marzuk et al., 1995; Ohberg et al., 1996; Rich and Isacsson, 1997). Tricyclic Antidepressants The tricyclic antidepressants are effective for the treatment of depressive symptoms. A tricyclic such as amitriptyline may be chosen in cases of suicidality due to its sedative effects, but the high risk of fatal outcome in overdose of tricyclics is a particular concern with regard to suicidal patients. Soloff et al. (1986) found that amitriptyline non-responders made more suicidal communications than placebo non-responders in a group of 29 borderline personality disorder patients. Other Classes of Antidepressants In terms of actual suicidal behavior, a prospective long-term, placebocontrolled treatment study of 1141 patients found more suicide attempts, including suicides in the group treated with the norepinephrine reuptake inhibitor maprotiline compared with placebo (Rouillon et al., 1989). While maprotiline was an effective antidepressant, it was associated with increased suicide attempts.

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Reducing Suicide: A National Imperative And Levin, a happy father and a man in perfect health, was several times so near suicide that he hid the cord, lest he be tempted to hang himself, and was afraid to go out with his gun, for fear of shooting himself. But Levin did not shoot himself, and did not hang himself; he went on living. —LEO TOLSTOY Anna Karenina

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