of CBT for depressed Latino youth and the only extant comparison of CBT and IPT for adolescent depression.

Diamond, Reis, Diamond, Siqueland, and Isaacs (2002) conducted a randomized clinical trial comparing Attachment-based family therapy (ABFT) with a wait-list control in 32 clinical referred adolescents meeting DSM-III-R criteria for major depression in a largely (69%) African-American, poor, inner-city sample. On average, subjects received eight sessions of ABFT, which focuses on strengthening family bonds, reduc-ing conflict, improving trust, improving cross-generational empathy, and, subsequently, improving affect regulation, communication, and promotion of competence. Those in the wait-list condition received 15 minutes of weekly telephone monitoring of their clinical condition as well as a face-to-face assessment at Week 6, at which point those still meeting criteria for major depression were offered ABFT. The treatment data from these latter cases were not included in the primary outcome analyses. At posttreatment, 81% of those treated with ABFT no longer met criteria for depression, compared to 47% in the wait-list control group. A significantly greater number of those assigned to ABFT reported a BDI <9 (62% vs. 19%). A significant treatment-by-time interaction favoring ABFT was found for interview-rated depression, self-reported anxiety, and child-reported parent–child conflict, with nonsignificant trends favor-ing ABFT for attachment to mother, suicidal ideation, and hopelessness.

One limitation of the study was that ABFT was 12 weeks in duration whereas the control treatment lasted 6 weeks, so that it is hard to differentiate time versus treatment effects. Therefore, analyses were conducted focusing on the first 6 weeks. While most of these analyses were not statistically significant, a significantly greater proportion of those treated with ABFT showed a BDI <9 by 6 weeks (56% vs. 19%). Fifteen of those treated with ABFT were followed up for 6 months after the end of treatment and only 13% had a depressive relapse. These results suggest that ABFT may be a promising treatment for ad olescent major depression, and that it is efficacious in a poor, African-American population. It is important to note, however, that in the one clinical trial comparing CBT with family therapy for depressed adolescents (Brent et al., 1997), family therapy produced significantly worse outcomes than CBT. The model of family therapy in the Brent et al. (1997) study focused on problem solving and communication, but it did not address attachment issues as in the study of Diamond et al. (2002).

Fine, Forth, Gilbert, and Haley (1991) compared two forms of short-term group therapy, either social skills training or therapeutic support, for depressed adolescents in a randomized clinical trial. Subjects in the therapeutic support group showed significantly greater reductions in clinical depression and significant increases in self-concept, although there were no group differences by 9-month follow-up. Subjects in the support group maintained their gains, and those who attended the social skills group caught up.

A high proportion of adolescent suicide attempters have mood disorders, and suicide attempts are a serious complication of mood disorder (Lewinsohn, Rohde, & Seeley, 1996). Therefore, we examine the three randomized clinical trials of adolescent suicide attempters that have been conducted thus far.

Rotheram-Borus et al. (1996) compared the efficacy of a cognitive behavior family therapy plus an emergency room intervention with that of family CBT alone. The family CBT plus emergency room intervention resulted in greater compliance with treatment. No baseline characteristics were reported, but end point analyses on maternal depression and general psychopathology, patient ideation, and parent-reported family interaction favored the combined intervention.

Harrington et al. (1998) compared a four-session, home-based family problem-solving intervention with treatment as usual for 162 adolescents who had taken an overdose. Subjects

were assessed at intake and at 2 and 6 months after intake. There were no differences between the two groups with respect to suicidal ideation, hopelessness, or family variables. A post-hoc subgroup analysis showed that nondepressed subjects who received the family intervention (vs. treatment as usual) reported lower suicidal ideation. However, the authors note that the depressed subgroup had much more severe ideation, so that the intervention was not effective in the more severely suicidal group.

Wood, Trainor, Rothwell, Moore, and Harrington (2001) randomized 63 adolescents who, prior to randomization, had made at least two suicide attempts within a year to either a six-session group intervention or to treatment as usual. The group treatment consisted of a combination of interpersonal skills training, anger management, problem solving, addressing of depression and hopelessness, and conflict resolution. In intent-to-treat analyses, those who received the experimental treatment were 6.3 times less likely to have made two or more attempts over an average of 29 weeks of follow-up (6% vs. 31%). Subjects in the experimental treatment were 60% less likely to make at least one attempt, although this effect was not statistically significant. They were also less likely to use routine care, had better school attendance, and had a lower rate of disruptive disorders than those who received treatment as usual. However, the two treatments did not differ in their effects on depression or global outcome.

Cognitive behavior therapy for youth depression appears to be more efficacious than no treatment, wait-list control, or attention placebo controls. There is also evidence in clinically referred samples that CBT can produce better results than alternate active treatments (Brent et al., 1997; Wood et al., 1996). Cognitive behavior therapy may also be “robust” in the face of many of the adverse clinical predictors of poor outcome (e.g., comorbidity) (Brent et al., 1998; Rohde et al., 2001). A recently completed benchmarking study has also suggested that much of the advantage of CBT found in clinical trials can be sustained in outpatient clinic settings (Weersing, Iyengar, & Birmaher, submitted). Efficacy also appears to be robust to format (group vs. individual), emphasis (behavioral vs. cognitive), and dose (5 to 16 sessions).

While these results are promising, many patients continue to have clinically significant levels of depression following CBT, and near majorities of patients experience at least one recurrence of depression within 2 years of treatment termination. It is perhaps not surprising that many patients (estimates range from 29% to 48%) seek additional services following acute CBT (Brent, Kolko, Birmaher, Baugher, & Bridge, 1999).

These studies provide some clues about the improvement of depression when CBT is used. Treatment with CBT fared more poorly in the face of maternal depressive symptoms, greater severity, and double depression; family discord also retarded recovery and predicted recurrence. Therefore, additional interventions that target maternal depression and family discord may well augment outcome. Moreover, particularly refractory and chronic conditions, such as double depression, may respond better to combinations of medication and CBT than to either as monotherapy alone, as suggested by comparable data in adults with chronic depression (Keller et al., 2000). Further work on improving outcome in patients with these poor prognostic risk factors needs to be conducted. There is little in the extant literature about the transportability of CBT to community settings. We do have evidence from benchmarking studies that CBT appears to be superior to community treatment and that it can yield similar results in clinical trials and in open treatment, under less controlled conditions (Weersing et al., 2003; Weisz & Weersing, 2002). We currently have very little information on the treatment of serious depression in preadolescents, and it is unclear how CBT may need to be adapted to take into account the more concrete cognitive style and greater dependence on parents seen in most preadolescent (as compared to adolescent) patients (Weisz & Weersing, 1999).

Much less is known about the efficacy of other forms of psychotherapy, such as interpersonal or family therapy. Interpersonal therapy for adolescents appears to be a promising treat

ment for adolescent depression and has been well accepted and efficacious in Latino populations. The one direct comparison of CBT and IPT is difficult to interpret, but IPT appeared at least as efficacious as CBT and with respect to some measures, more so (Rossello & Bernal, 1999). With additional studies of IPT it will be important to understand which factors predict good and poor response.

Despite numerous studies implicating family factors in adolescent depression, there have only been two studies that examine the efficacy of family therapy in child or adolescent depression. A skills-based family treatment did not appear to be as efficacious as CBT, whereas ABFT that focused on repairing and strengthening emotional bonds achieved results that were as good as those either with CBT or IPT-A (Brent et al., 1997; Diamond et al., 2002). This treatment mode clearly requires further study.

Relatively few studies have examined the impact of psychosocial intervention on the prevention of recurrent suicidal behavior, in part because those teens at higher risk for recurrence of suicide attempt are usually excluded from treatment trials for adolescent depression. The few studies that have been conducted are not definitive but suggest some utility for family cognitive behavior approaches and skills training. This vulnerable population deserves further scrutiny and study.

At this time the first line medication treatment for adult MDD is the SSRIs, which include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro). They have a greater affinity for the serotonin transporter than for the noradrenergic transporter, and each compound selectively inhibits 5-hydroxytryp-tamine (5-HT) reuptake and has unique secondary binding properties. This class of drug is rarely associated with fatalities and given its safety profile provides an easy treatment option for the clinician (Farvolden, Kennedy, & Lam, 2003).

The latest generation of antidepressants is the selective serotonin and noradrenaline reuptake inhibitors (SNRIs), such as venlafaxine (Effexor), duloxetine (Cymbalta), and milnacipran. It appears that venlafaxine possesses a selective high affinity for the noradrenergic and sertonergic reuptake sites; however, it is only at higher doses (150 to 225 mg) that its noradrenergic reuptake becomes activated. This dual reuptake inhibition may contribute to the high rates of remission of depressive symptoms compared to those with SSRIs (Thase, Entsuah, & Rudolph, 2001). Although venlafaxine's side effect profile is similar to that of SSRIs, at higher doses >200 mg there is a 5.5% clinically significant elevation of blood pressure and at higher doses >300 mg the incidence of hypertension reaches 13%. Duloxetine is a newer SNRI with reportedly dual reuptake inhibition that is equal at clinical doses. Reboxetine is a selective norepinephrine reuptake inhibitor not approved in the United States for the treatment of major depression. Mirtazapine, which belongs to the piperazine-azepine group of compounds, has not been investigated in the treatment of pediatric depression.

Another novel compound used for the treatment of adult depression is bupropion, which has it effects by blocking noradrenergic and do

pamine reuptake (Dong & Blier, 2001). It has the side effects of insomnia, nausea, increased anxiety, and restlessness. Another potential side effect is an increased incidence of seizures, which occur at a rate of 0.4% with daily doses below 450 mg and 2.4% with daily doses between 450 and 600 mg (Johnston et al., 1991). However, one important advantage of this compound in treating adults is that it has been found to cause no weight gain or sexual dysfunction.

Nefazodone and trazodone inhibit the 5-HT2A receptors. This class of compounds is effective for the symptom of insomnia; however, sedation is a common problematic side effect along with orthostatic hypotension. A common clinical practice is to use low doses of trazodone for insomnia while simultaneously starting an SSRI. Trazodone is associated with a rare side effect of priaprism. In addition, hepatic toxicity and liver failure have been found to be associated with these compounds.

Older classes of antidepressants efficacious in treating adult MDD, such as the tricyclic and heterocyclic antidepressants (amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, and protriptyline) inhibit different combinations of serotonin, noradrenergic, and dopamine receptors. Their antagonism at other receptor types causes difficult side effects such as dry mouth, confusion, orthostatic hypotension, tachycardia, weight gain, urinary retention, and constipation. In addition, doses outside of the therapeutic range may be lethal because of conduction abnormalities. The MAOIs (phenelzine and tranylcypromine) irreversibly inhibit the monoamine oxidase isozymes A and B. It is thought that the blockade of the isozyme A lends these compounds their clinical efficacy (Mann et al., 1989). One major issue with this class of antidepressants is the required tyramine-restricted diet, which if not adhered to can prove to be fatal with dangerous elevation of the patient's blood pressure. Also, drugs that increase synaptic monoamines must be avoided, such as over-the-counter cold medications, TCAs, SSRIs, stimulants, and cocaine. There is also a risk of lethal, rare hyperthermic reactions that occur with meperidine and other opiates. Given these issues of tolerability and potential serious adverse events, TCAs and MAOIs have been more often reserved as second-and third-line agents for patients who have failed treatment with one of the newer antidepressant classes.