prove basic social skills and effective coping. Participants (N = 264) were randomly assigned to either the experimental intervention or a treatment-as-usual condition involving long-term outpatient treatment. In a 2-year follow-up, Rudd et al. found that participants in both groups showed significant reductions in suicidal ideation and behavior and experienced stress, and improvements in self-appraised problem-solving ability. The intensive time-limited intervention was found to be more effective than long-term treatment in retaining the highest-risk participants. Subsequent analyses showed that patients with psychiatric symptomatology experienced the most improvement in response to this intervention (Joiner, Voelz, & Rudd, 2001). The rate of suicide attempts at follow-up was not reported for either the experimental or control group, however, and conclusions were limited by high attrition rates in both the experimental and control group.

Harrington and colleagues in Great Britain (Byford et al., 1999; Harrington et al., 1998, 2000) developed a home-based family intervention for adolescents with a history of deliberate self-poisoning. This intervention used a cognitive behavioral approach to address family dysfunction assumed to be related to the suicide attempt (Kerfoot, 1988; Keerfoot, Dyer, Harrington, Woodham, & Harrington, 1996), and to improve adherence to treatment by bringing it into the home. The intervention consisted of five highly structured sessions focusing of goal setting, reviewing the self-poisoning episode, communication, problem solving, and discussing issues related to the family. The program included a treatment manual and videotape for training.

This brief intervention was found to be effective primarily among those adolescents who were not seriously depressed and had less severe suicidal ideation, who made up about one third of the 85 participants (Harrington et al., 1998, 2000). Adherence and parental satisfaction with treatment were better for participants in this treatment relative to treatment as usual. The intervention was found to be no more costly than routine care alone (Byford et al., 1999).

Wood and colleagues have developed an additional psychotherapeutic variant, using developmental group therapy as an alternative to usual care for adolescents who have repeatedly attempted to harm themselves (Wood, Harrington, & Moore, 1996; Wood, Trainor, Rothwell, Moore, & Harrington, 2001). The group-therapy format was hypothesized to be useful in providing an arena for working on social problem-solving and relationship skills that are often considered core to suicidal behavior. Using a developmental approach to address issues unique to adolescents, the intervention combines problem-solving and cognitive behavioral interventions (Harrington, et al., 1998), DBT (Linehan et al., 1991), and psychodynamic approaches. An acute phase focusing on core themes (family and peer relationships, school problems, anger management, depression, self-harm, and hopelessness) is followed by a longer phase that concentrates on group processes. In interviews conducted about 7 months after treatment began, participants in the developmental group therapy reported engaging in less self-harm than did adolescents who received routine care, although depression did not appear to improve. Episodes of self-harm became less frequent as participants attended more sessions of the group therapy, whereas among those in usual care, self-harm behaviors were found to increase compared to baseline. Participants in the developmental group therapy, particularly youth who had made multiple suicide attempts, also showed reductions in conduct problems.

Considering suicidal behavior as the primary problem rather than the symptom, Henriques, Beck, and Brown (2003) have developed and examined a brief cognitive intervention for suicide attempters ages 18 and over. The intervention consists of 10 sessions, beginning with the identification of proximal thoughts and associated core beliefs that were activated just prior to the adolescent's suicide attempt. Cognitive and behavioral strategies are then applied to help individuals develop more adaptive ways of thinking about their situation and more functional ways of responding during periods of acute emotional distress. Specific attention is given to the role of hopelessness.

The intervention follows a structured protocol with specific therapeutic strategies developed for the early, middle, and late phases of treatment, which are designed for replication by mental

health professionals working with suicidal youth. Early sessions focus on engaging the patient, setting goals, and increasing hopefulness. Middle sessions involve changing maladaptive beliefs and addressing problem-solving deficits and impulsivity while developing reasons for living, increasing adherence with health-care professionals, and increasing social support. Later sessions focus on relapse prevention, terminations, therapy extensions, and booster sessions as necessary. The efficacy and effectiveness of the intervention are currently being evaluated in a randomized controlled clinical trial. To date, the approach has not been used in the treatment of younger adolescents.

In another variation, Miller and colleagues (Miller et al., 1997; Rathus & Miller, 2002) have used a modification of DBT in their treatment of adolescent suicide attempters who demonstrated at least three features of BPD. The intervention developed by Miller et al. consists of 12 weeks of twice-weekly individual and family skills training. In one specific trial (Rathus & Miller, 2002), participants in the DBT group were found to have better adherence to treatment and fewer hospitalizations than those receiving treatment as usual, despite the fact that they had greater psychiatric comorbidity than control subjects. The DBT treatment was also found to be associated with reduced suicidal ideation, symptom severity, and distress. Although suicide attempts were less likely in the DBT group than among controls, this difference was not found to be significant.

Results reported to date suggest the effectiveness of cognitive behavioral interventions in improving social functioning and reducing suicidal ideation among suicidal adolescents, particularly those with mild to moderate depression and those with borderline features. In some cases, however, the outcomes of experimental treatments have not been substantially better than those obtained by comparison or standard care treatments. Long-term effects of psychotherapy interventions on suicidal behavior have not yet been reported. Given that maladaptive cogni tions and behaviors have likely developed over a long period of time, it is not clear that short-term psychotherapies will ultimately be found to be effective in reducing suicidal behavior.

The neurobiological underpinnings of suicidal behavior are currently the subject of considerable research, and new information that broadens our understanding of this complex area continues to emerge. Recent reviews have identified serotonergic dysfunction, noradrenergic dysfunction, dopaminergic dysfunction, and hypothalamic–pituitary–adrenal (HPA) axis hyperactivity as the key neurobiological correlates of suicidality (Mann, 2003; Nemeroff et al., 2001).

The most extensively replicated studies have focused on the role of serotonergic dysfunction. Studies have reported that depressed patients who have made suicide attempts have lower levels of 5-hydroxyindoleacetic acid (5-HIAA) in the brainstem and in cerebrospinal fluid (CSF) compared to depressed nonattempters (Nemeroff et al., 2001). Decreased CSF 5-HIAA is hypothesized to be a marker of the impulsive, aggressive, and violent nature of suicide, and appears to correlate with a high degree of suicidal planning and a high level of lethality of suicide attempts. Central nervous system (CNS) serotonergic dysfunction has also been associated with suicidal behavior.

One early small RCT study of adult chronic suicide attempters (Montgomery et al., 1979) found that depot neuroleptic medications were effective in preventing repetition of suicidal behavior, although patient reluctance and negative side effects were noted as limitations. Hawton and colleagues, in their exhaustive search using Cochrane criteria (1998), were unable to identify any other RCT conducted through the mid-1990s that found antidepressant medications to be effective in preventing subsequent suicidal behavior in patients who had made prior attempts. They noted, however, that the only antidepressants that had been systematically stud

ied for suicide-related outcomes, nomifensine and mianserin, had been discontinued for general use at the time of their review.

A number of studies have reported decreased suicidality among mood-disordered adult patients receiving long-term lithium treatment (Sharma, 2003; Tondo, Jamison, & Baldessarini, 1997). Pooling results reported by several individual studies conducted between 1974 and 1996, Tondo and colleagues estimated that lithium treatment was associated with an almost 9-fold reduction in risk of suicide and suicide attempts. They noted that it is not clear whether the protection lithium provides against suicide derives from its general mood-stabilizing effect or its effects on reducing aggression and impulsivity through improved serotonergic functioning.

Long-term treatment with clozapine, an atypical antipsychotic, has been shown to produce similar effects among patients with schizophrenia, reducing suicidal behavior among this high-risk population (Sharma, 2003; Spivak, Shabash, Sheitman, Weizman, & Mester, 2003). Randomized controlled trials involving both lithium and clozapine are needed to determine the extent to which positive outcomes are related to patient characteristics that are correlated with their ability to adhere to long-term treatment.

Among patients suffering from unipolar depression, selective serotonin reuptake inhibitors (SSRIs) are currently considered superior to other antidepressants for improving both suicidal behavior and suicidal ideation (Nemeroff et al., 2001). Although no large RCTs of SSRIs have included outcomes related to suicide (due to the exclusion of suicidal patients from most pharmaceutical-sponsored trials), there is considerable evidence pointing to the positive effects of such medications on the CNS seroto-nergic dysfunction noted above to be associated with suicidality in adults (Oquendo, Malone, & Mann, 1997).

In recent years, several European studies have reported inverse correlations between use of SSRIs and suicide deaths, suggesting their potential significance for reducing suicide risk (Barbui, Campomori, D'Avanzo, Negri, & Garattini, 1999; Carlsten, Waern, Ekedahl, & Ranstam, 2001; Gunnel, Middleton, Whitley, Dorling, & Frankel, 2003; Isacsson, 2000). Although large RCTs need to be conducted to determine causative linkages, SSRIs appear to be a potent means of treating suicidality. The SSRIs have been reported to have less inherent toxicity than the previously widely used tricyclic antidepressants (TCAs), and are thus less likely to be related to death from overdoses. Although side effects such as gastrointestinal upset, insomnia, and sexual dysfunction are fairly common, most SSRIs appear to be well tolerated.

To date there are few publicly reported studies involving the use of pharmacological interventions to treat suicidal behavior among young people. Although the effectiveness of antidepressants in treating children and adolescents has not been definitively established, use of SSRIs in treating depressed and suicidal youth has nonetheless become widespread. A recent U.S. analysis by Olfson, Shaffer, and colleagues (2003) reported an inverse relationship between regional change in use of antidepressants among youth aged 10–19 and suicide mortality. The relationship was found to be significant specifically among males, among youth aged 15–19, and in geographic regions with lower family median incomes.

Although these studies do not establish use of antidepressants to be causally linked to decreases in suicide deaths, some efforts are under way to implement and evaluate pharmacological treatments among youth with serious psychopathology, including suicidal ideation or behavior. The key assumption of these efforts is suicide risk among youth, as in adults, can be reduced through the use of antidepressant medications.

An intervention by Cornelius and colleagues used fluoxetine (Prozac) to treat adolescents with comorbid major depression and an alcohol use disorder, including some who demonstrated sui-cidal ideation at baseline (Cornelius, Bukstein, et

al., 2001). The intervention was based on findings that reducing depression and problem drinking in adults resulted in a reduction of suicidal behavior (Dinh-Zarr, Diguiseppi, Heitman, & Roberts, 1999). Cornelius and colleagues also found fluoxetine to be effective in treating suicidal adults with an alcohol use disorder. Such treatment improved but did not completely eliminate both depressive symptoms (including suicidal ideations) and the level of drinking (Cornelius, Salhoum, Lynch, Clark, & Mann, 2001).

In their studies involving youth, all patients receiving fluoxetine improved with respect to depressive symptoms, and over half improved in symptoms of alcohol dependence. Among participants with suicidal ideation at baseline, ideation decreased and these decreases remained 1 year after treatment (Cornelius, 2003). Cornelius reported no serious adverse effects of fluoxetine among youth.

A definitive study supported by the National Institute of Mental Health, known as the Treatment of Adolescents with Depression Study (TADS), has provided the strongest evidence to date of the effectiveness of fluoxetine in treating adolescent depression and suicidality. This study randomly assigned 439 youths ages 12 to 17 diagnosed with moderate to severe depression to one of four treatment conditions for a period of 36 weeks: fluoxetine therapy alone, cognitive-behavioral therapy (CBT) alone, fluoxetine and CBT, and a placebo drug treatment. Based on the results obtained during the first 12 weeks of the study, the highest rate of clinical improvement (71%) was found among those receiving the combination treatment, followed by 61% of those who received fluoxetine alone, 43% of those who received CBT alone, and 35% of those who received the placebo drug treatment (March et al., 2004). It should be noted that the most seriously suicidal adolescents were excluded from the TADS sample, and thus only 29% of participants reported having clinically significant suicidal ideation at baseline. This percent decreased to 10% by week 12. Although no suicides occurred during the trial, the risk of a suicide attempt among study participants during the first weeks on fluoxetine was reported to be twice that for participants not receiving the medication. The study investigators concluded, how ever, that the benefits of the medication far outweighed its associated risk.

Since fluoxetine is presently the only antidepressant medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of major depression in children and adolescents, the findings reported by Cornelius and colleagues and by the (NIMH) study have important implications for suicide prevention among depressed youth. It is encouraging that publicly supported large-scale RCTs are beginning to be undertaken. Much additional research is needed, however, to further illuminate the impact of fluoxetine, as well as that of other medications, for reducing suicidal ideation and behavior among both substance-abusing and nonabusing adolescents.

Since 2003, concerns have been raised about the safety of the newer antidepressant medications for use by children and adolescents, based initially on unpublished data from drug company studies linking use of SSRIs by children and adolescents to suicidal ideation and self-harm behaviors. In late 2003, these reports led the British drug regulatory agency to recommend against the use of all SSRIs except fluoxetine in treating depression among youth under age 18 (Goode, 2003).

In 2004, the U.S. Food and Drug Administration undertook a review of 23 clinical trials involving the use of nine different antidepressant medications by over 4,000 children and adolescents. The results of this analysis, presented in September 2004, found that the medications increased the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder (MDD) or other psychiatric disorders (Hammad, 2004). Specifically, 4% of all youth taking medication reported an “adverse event,” i.e., thoughts of suicide and/or potentially dangerous behavior, compared to 2% of those taking a placebo drug.

On October 15, 2004, the FDA directed pharmaceutical companies to label all antidepressant medications distributed in the U.S. with a black box warning to this effect (FDA, 2004), even