Mood disorders, including depression and bipolar disorders, are the most common psychiatric comorbidities among patients with substance use disorders.

Treating patients’ cooccurring mood disorders may reduce their substance craving and taking and enhance their overall outcomes. A methodical, staged screening and assessment can ease the diagnostic challenge of distinguishing symptoms of affective disorders from manifestations of substance intoxication and withdrawal.

Treatment should maximize the use of psychotherapeutic interventions and give first consideration to medications proven effective in the context of co-occurring substance abuse.

Expanded communication and collaboration between substance abuse and mental health providers is crucial to improving outcomes for patients with these complex, difficult co-occurring disorders.

Mood or affective disorders, as defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), are classified as depressive or bipolar (Table 1).

During the past decade, research results and clinical experience have converged in the recognition that these psychiatric illnesses commonly co-occur with substance use disorders (SUDs) and that the combination has adverse clinical consequences.

Mood and SUD comorbidity downgrades the clinical course, treatment outcome, and prognosis for each problem. Theoretically, the converse is also likely to be true: Successful alleviation of one condition should facilitate recovery from the other. Some evidence indicates that treating a comorbid affective disorder can decrease substance abuse and craving (Cornelius et al., 1997).

Researchers and clinicians have begun to develop treatment approaches that address both disorders simultaneously, with early indications of efficacy.

This article explores the prevalence and relationship of co-occurring mood disorders and SUDs, describes a methodical approach to assessment, and reviews evidencebased psychotherapeutic and pharmacotherapeutic treatments.

EPIDEMIOLOGICAL RELATIONSHIPS

Two epidemiological studies have examined the prevalence of psychiatric and substance use disorders by conducting diagnostic interview surveys in representative community samples of adults: the National Institute of Mental Health Epidemiologic Catchment Area (ECA) Study (Regier et al., 1990) conducted in the early 1980s and the National Comorbidity Survey (NCS) conducted in 1991 (Kessler et al., 1994).

Both provided striking documentation that mood disorders increase the risk of SUD. In the ECA Study, the lifetime prevalence rate for any non-SUD mental disorder was estimated to be 22.5 percent, compared with 13.5 percent for alcohol abuse/dependence and 6.1 percent for other drug abuse/dependence (Regier et al., 1990).

Among individuals with a mood disorder, 32 percent had a cooccurring SUD. Of individuals with lifetime major depression, 16.5 percent had an alcohol use disorder and 18 percent had a drug use disorder. SUDs were particularly common among individuals with bipolar disorder—56 percent had a lifetime SUD.

In the NCS, the lifetime prevalence estimate for any mental disorder was 48 percent (Kessler et al., 1997). The estimate for alcohol dependence was 14.1 percent, and for drug dependence 7.5 percent. The lifetime prevalence rate for any mood disorder was 19.3 percent.

Compared with individuals with no mood disorders, those with depression were approximately twice as likely, and those with bipolar disorder approximately seven times as likely, to have an SUD. (The ECA study also documented a high rate of co-occurrence of SUD, mood, and anxiety disorders; while anxiety disorders are clinically common and important, they are a separate category of illness and discussion of them is beyond the scope of this paper.)

Studies of individuals seeking treatment have resulted in variable estimates of the comorbidity of mood disorders and SUDs. Among those seeking treatment for alcohol dependence, an estimated 20 to 67 percent had experienced depression and 6 to 8 percent had experienced a bipolar disorder at some time in their lives (Brady, Myrick, and Sonne, 1998).

In samples of cocaine-dependent individuals, the corresponding estimates have ranged between 30 and 40 percent and between 10 and 30 percent.

Rounsaville and colleagues (1991), after assessing 298 cocaine abusers seeking treatment, reported that 44.3 percent had a current mood disorder and 61 percent had a history of mood disorders; 30.5 percent had had at least one episode of major depression and 11.1 percent at least one episode of mania or hypomania.

Bipolar disorder appears to be more prevalent among cocaine-dependent individuals than alcoholdependent individuals (Sonne and Brady, 1999).

One reason for the differences in reported prevalence rates is the complexity of diagnostic issues at the interface of mood disorders and SUDs.

For example, because abstinence from drugs can temporarily depress mood, a patient who is evaluated while in withdrawal may be misdiagnosed as suffering from a mood disorder. Clinicians may reach different conclusions, depending on when they conduct assessments relative to the patient’s entry into treatment.

WHY ARE THESE COMORBIDITIES SO COMMON?

The major mood disorders and their key clinical features can be found in Table 1. Several theories have been proposed to explain the high co-occurrence of substance abuse and mood disorders.

In general, they fall into three categories.

Disorder Fostering Disorder

One theory proposes that the pathological effects of a mood disorder or SUD may increase risk for the other. For example, mood disorders may motivate individuals to resort to drugs and alcohol to cope with their negative affective states.

Such an explanation would jibe with clinicians’ everyday experience of individuals with SUDs saying they use drugs and alcohol to combat unwanted moods. The substances may initially minimize or moderate the mood symptoms, but withdrawal and chronic abuse typically exacerbate mood degradation, leading to increasing abuse and ultimately dependence.

The self-medication explanation implies that individuals will tend to select drugs that alleviate their specific psychiatric symptoms. For example, some psychologists suggest that people with uncontrollable feelings of rage and aggression may choose opiates for these drugs’ mellowing effects, while people who are depressed may take cocaine because it exhilarates and energizes them.

Studies showing such associations between abusers’ drugs of choice and their psychiatric diagnoses or symptoms would strengthen the evidence for the self-medication model, but to date few have been published.

While the self-medication model suggests that mood disorders increase the risk of substance abuse, the converse is also possible.

Chronic substance abuse sometimes “unmasks” bipolar or other mood disorders— that is, triggers an increase in symptom severity from a subclinical to a clinically significant level.

This appears to occur because in genetically vulnerable individuals, the drugs exacerbate pathophysiological changes in neurotransmitter systems or signaling pathways that already are abnormal and underlie the mood disorder (Markou, Kosten, and Koob, 1998).

Overlapping Neurobiological Pathways

Another proposed explanation for the high comorbidity rate of mood disorders with SUDs involves “kindling.” The term, usually associated with epilepsy, refers to the concept that repeated disruptions, such as occur during seizures, sensitize brain cells.

The more sensitized the neurons become, the less it takes to disrupt them, which is why in untreated epilepsy, seizures tend to become more frequent and severe over time.

Both alcohol and cocaine sensitize neurons, and this increased sensitivity may contribute to the typical progression from occasional to increasingly frequent and intense use of these substances.

Mood disorders often follow a similar course of increasingly distressing symptomatic episodes separated by progressively shorter periods of remission, suggesting that they too may intensify via a kindling process (Post, Rubinow, and Ballenger, 1984).

The kindling explanation for comorbidity, then, holds that in vulnerable individuals, an underlying neurobiological tendency to sensitization may promote both drug dependence and mood disorders.

Underlying Genetic Factors

Research has definitively shown that both substance abuse and mood disorders have genetic risk factors. In addition, families with substance abusers are more likely than those without to also have members with mood disorders, and vice versa.

These facts raise the possibility that some gene variants may contribute to the risk for both types of illness.

A person’s genes might:

• make him or her vulnerable to mood disorders, which he or she might then try to self-medicate, as discussed above;

• shape the brain so that it responds to initial drug exposures in ways that promote chronic substance abuse, with the drugs then wreaking changes that lead to mood disorders;

• cause the brain to develop in a way that directly fosters both types of disorder, for example through vulnerability to neuronal sensitization and kindling.

Diagnostic Confounding

Some portion of the reported high co-occurrence of SUD and mood disorders may represent confounding of mood disorders and transient symptoms related to acute abuse and withdrawal.

Drug abuse symptoms can mimic symptoms of both depression and mania. Acute alcohol and stimulant intoxication can produce symptoms of mania or hypomania, and substance withdrawal often manifests as symptoms of dysphoria and depression.

Chronic use of central nervous system (CNS) stimulants, such as cocaine and amphetamines, may produce symptoms that are typical of bipolar spectrum disorders, such as euphoria, increased energy, decreased appetite, grandiosity, and paranoia.

Conversely, withdrawal from CNS stimulants (especially cocaine) can give rise to anhedonia (inability to feel pleasure), apathy, depressed mood, and suicidal ideation.

Chronic use of CNS depressants (e.g., alcohol, benzodiazepines, barbiturates, and opiates) can lead to depressive symptoms such as poor concentration, anhedonia, and problems sleeping, while withdrawal from these drugs can result in anxiety and agitation.

The more subtle affective disorders such as dysthymia and cyclothymia are particularly difficult to differentiate from symptoms of SUD. It remains unclear which, if any, of the models discussed explain the high comorbidity between mood disorders and SUDs.

The relationship is complex and bidirectional, suggesting an ongoing interaction between these disorders; having one may affect the vulnerability to developing the second or change its clinical course. 

Continued - see source document http://www.nida.nih.gov/PDF/Perspectives/vol3no1/MoodDis.pdf