Guideline:

3 Depression Co-Occurring with Other Psychiatric Conditions

Guideline: Patients with depressive symptoms or in a major depressive episode may also be suffering from another nonmood psychiatric disorder. Treating one of the two disorders often clarifies the diagnostic picture. If the nonmood disorder is causing the mood symptoms, the nonmood disorder should usually be treated first. When formal major depressive syndrome is associated with another psychiatric condition, the decision of which to treat first rests on the nature of the nonmood disorder:

■ If the nonmood disorder is an eating or obsessive-compulsive

disorder (OCD), that is usually the initial treatment target. (Strength of Evidence = A.)

■If the nonmood disorder is generalized anxiety or personality

disorder, the major depressive disorder is the first treatment target, because patients with either of these two nonmood conditions are not typically excluded from randomized controlled treatment trials of major depressive disorder. (Strength of Evidence = B.) ■ If the associated nonmood condition is panic disorder, the

practitioner must decide which is primary by considering the patient's personal or family history, as well as by gauging which of the two conditions is causing the greater impairment. (Strength of Evidence = B.)

Figure 4 provides an algorithm for deciding when to treat depression in the presence of a concurrent nonmood psychiatric condition.

Alcohol/Drug Abuse or Dependency

Guideline: Alcoholism and major depressive disorder are distinct clinical entities. They are not different expressions of the same underlying condition. While alcoholism is rarely a consequence of depression, many alcoholics do develop depressive symptoms or the full syndrome of major depression. (Strength of Evidence = B.)

The following conclusions are tentatively applicable to primary care settings since no data were found on depression in alcoholic patients seen in primary care settings or in alcoholics self-referred to self-help groups such as Alcoholics Anonymous. Most studies are of patients seen in psychiatric settings, who may be more likely to have other psychiatric

Figure 4. Relationship between major depressive and other current psychiatric disorders

1When the depression is treated, the anxiety disorder should resolve as well.

2Choose medications known to be effective for both the depression and the other psychiatric disorder.

3Primary is the most severe, the longest standing by history, or the one that runs in the patient's family.

*In certain cases (based on history), both major depression and substance abuse may require simultaneous treatment.

problems in addition to alcoholism. Furthermore, the diagnostic criteria for alcoholism have become more inclusive over the last 15 years.

Nine studies have examined the extent to which patients with primary depression develop alcoholism (Deykin, Levy, and Wells, 1987; Hasin, Grant, and Endicott, 1988; Lewis, Helzer, Cloninger, et al., 1982; Powell, Read, Penick, et al., 1987; Robins, Gentry, Munoz, et al., 1977; Schuckit, 1983, 1985; Winokur, Reich, Rimmer, et al., 1970; Woodruff, Guze, Clayton, et al., 1973). Most revealed that alcoholism is rarely a consequence of depression; it occurs in less than 5 percent of patients. Overall, the prevalence of alcoholism in patients with primary depression is probably no higher than in the general population.

On the other hand, most studies have found that alcoholics do become depressed over time. Of the 24 studies reviewed, most found that between 10 and 30 percent of patients with alcoholism also suffered from depression at the time of evaluation (see Petty, 1992, and Depression Guideline Panel, forthcoming).

The ECA Study found the prevalence of alcoholism to be approximately 5 percent (Helzer and Pryzbeck, 1988). This study also found the odds ratio for the coexistence of depression and alcoholism to be 1.7. That is, persons in the community who met the diagnostic criteria for alcoholism were nearly twice as likely as those without alcoholism to meet the criteria for major depressive disorder.

Based on the ECA data reanalysis commissioned by the panel, 10 percent of those with major depressive disorder and a concurrent psychiatric condition (n = 31) had alcohol abuse as the second condition. For those with dysthymic disorder complicated by another psychiatric condition (n = 46), 30 percent abused alcohol. For those with DNOS and another psychiatric condition (n = 167), 67 percent abused alcohol. Thus, practitioners should always inquire about co-morbid alcohol and drug abuse or withdrawal in those with mood syndromes and symptoms.

The idea that depressed patients self-medicate with alcohol and, therefore, become alcoholic seems untrue for men, but may be true for some women. The few studies (Depression Guideline Panel, forthcoming) that focused specifically on women suggest that women alcoholics (perhaps as many as one in four) may be more likely to have had a preexisting mood disorder. They may also be more likely to develop depression as a consequence of prolonged heavy drinking, perhaps twice as often as their male alcoholic counterparts. Women reared by alcoholic fathers appear to be at greater risk for depression (Goodwin, Schulsinger, Knopf, et al., 1977).

Although family studies have provided strong evidence that alcoholism and major depressive disorder are independently transmitted, a family history of depression and alcoholism may be associated with a poorer prognosis for the alcoholism. However, there is no evidence for familial aggregation between alcoholism and depression. Adoption studies confirm the independent transmission of depression and alcoholism. Goodwin and

colleagues (Goodwin, Schulsinger, Hermansen, et al., 1973; Goodwin, Schulsinger, Knopf, et al., 1977) found an increased incidence of alcoholism in both the adopted sons and daughters of alcohol abusers, but no increase in the incidence of depression. They also found that daughters of alcoholics reared by their biologic parents were more likely to experience depression as adults. This suggests that the environment can contribute to the development of depression, particularly in women. Two studies suggest an important additive interaction between alcoholism and depression (von Knorring, Bohman, von Knorring, et al., 1985; Zisook and Schuckit, 1987). It may be that the familial contribution of mood disorder to alcoholism indicates a poorer prognosis for the alcoholism.

The clinical course of depression with alcoholism has not been extensively studied. Available data from four studies suggest that most patients admitted to alcoholism treatment programs who also have clinical depression experience spontaneous remission of their depressive symptoms during the first 2 to 4 weeks of sobriety (Brown and Schuckit, 1988; Dorus, Kennedy, Gibbons, et al., 1987; Schuckit, 1983, in press; Willenbring, 1986). Depressive symptoms and syndromes seen in very recently detoxified alcoholics likely reflect the toxic effects of alcohol consumption.

The longer term course of illness for depression with alcoholism is more difficult to assess. Two studies that followed patients for more than a year determined that the existence of depression and alcoholism at initial assessment predicted a poorer outcome for the alcoholism, at least in men, 1 year later (Loosen, Dew, and Prange, 1990; Rounsaville, Dolinsky, Babor, et al., 1987). One 2-year followup study found no difference in alcoholic symptoms in patients with major depressive disorder plus alcoholism versus those with alcoholism alone at initial assessment (O'Sullivan, Rynne, Miller, et al., 1988). No lengthier followup studies are available.

For logistical reasons, the panel did not formally review the area of depression with drug abuse or dependency. However, depressive symptoms or major depressive episodes can occur concurrently with drug abuse. Intoxication with brain depressants is known to cause dysphoric mood and even suicidal ideation. Withdrawal from stimulants, such as cocaine or amphetamines, produces sadness, insomnia, apathy, and other depressive symptoms. The course and response to treatment of depressive disorders in patients who abuse drugs may differ from those of depressive disorders in patients who do not have substance dependency. In the ECA data reanalysis, drug abuse was the second condition in 19 percent of the 31 individuals with major depressive disorder and another psychiatric condition, in 30 percent of the 46 with dysthymic disorder and another condition, and in 26 percent of the 167 with DNOS and another psychiatric condition. Substance abuse is common in those with depressive syndromes and symptoms.

Guideline: It is recommended that depressed patients with concurrent substance abuse discontinue the abused substance and their condition be reevaluated 4 to 8 weeks later when they are in a drug-free state. If major depressive disorder is still present, it is treated as a primary mood disorder. In certain clinical situations, however, earlier treatment of the depression may be needed. (Strength of Evidence = = B.)

Anxiety Disorders

Guideline: Depressive symptoms or syndromes often accompany anxiety, panic, or phobic disorders. Furthermore, anxiety symptoms are frequent in major depressive episodes. The depression may precede the panic or anxiety disorder, or the anxiety disorder may be the forerunner of and part of the longitudinal course of a mood disorder. The presence of both anxiety/panic and a major depressive disorder results in a more severe disorder with greater impairment than does either disorder alone. When the patient complains of anxiety symptoms, major depressive symptoms should be elicited. (Strength of Evidence A.)

Concurrent panic disorder is present in 10 to 20 percent of patients with major depressive disorder seen in ambulatory treatment settings. In possibly half of these, the panic disorder preceded the major depressive disorder. About 30 percent of outpatients with major depressive disorder may also have met the criteria for generalized anxiety disorder sometime during the course of their illness. In about half of these, the generalized anxiety disorder preceded the major depressive disorder.

Four community studies (Angst and Dobler-Mikola, 1985; Boyd, Burke, Gruenberg, et al., 1984; Hecht, von Zerssen, and Wittchen, 1990; Vollrath, Koch, and Angst, 1990) and one conducted in a primary care setting (Katon, Vitaliano, Russo, et al., 1986) have reported current comorbidity of anxiety and mood disorders using DSM-III or DSM-III-R. In the ECA data reanalysis (Johnson and Weissman, unpublished manuscript), panic disorder was found in 19 percent of the 31 people with major depressive disorder and another psychiatric condition, in 7 percent of the 46 people with dysthymic disorder and another condition, and in 21 percent of the 167 people with DNOS and another psychiatric condition.

Most longitudinal studies of patients with anxiety disorders have found an increased incidence of depressive disorders over time. In one study, 91 percent of patients with agoraphobia developed a mood disorder over the 3-year followup (Munjack and Moss, 1981). Eighty-four percent of these patients had a family history of probable mood disorder. One study found that two-thirds of a group with agoraphobia or panic disorder developed major depressive disorder, 85 percent of which was of the melancholic type (Breier, Charney, and Heninger, 1985). Approximately half of those