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Substance Use Disorders: Sex Differences and Psychiatric Comorbidities
Prevalence Rates of Psychiatric Comorbidity With Other Drug Use Disorders
General Population Samples. Data from the ECA study show that 76% of men and 65% of women with drug abuse or dependence present at least 1 other lifetime psychiatric diagnosis (including lifetime alcohol abuse or dependence). When one excludes alcohol abuse or dependence, however, the overall psychiatric comorbidity is higher for women than for men. For example, prevalence rates were higher for men regarding comorbid alcohol abuse or dependence and APD, but higher for women regarding comorbid mood disorders (major depression, dysthymia, and mania), anxiety disorders (panic, obsessive–compulsive, and phobic disorders), and schizophrenia (24).
Merikangas and colleagues investigated patterns of psychiatric comorbidity in substance use disorders (including both alcohol and other drugs) (25). These authors combined surveys from Canada, Germany, Mexico, and the Netherlands, in addition to the NCS. Their analysis included mood and anxiety disorders, along with antisocial behaviour and CDs. They observed that overall psychiatric comorbidity was higher for drug use disorders than for alcohol use disorders and that men and women tended to have similar comorbidity patterns. However, in specific sites, women tended to be associated with higher comorbidity rates, particularly where substance use severity levels were lower.
Treatment Samples. Studies of treatment-seeking individuals with cocaine dependence report that women are more likely than men to be diagnosed with depression and phobias, whereas men have higher rates of alcohol dependence, attention-deficit hyperactivity disorder (ADHD), and APDs (26–28).
These results have been confirmed in more recent studies of treatment-seeking individuals with drug dependence (particularly, among those with opiate and cocaine dependence): higher rates of alcohol dependence, APDs, and ADHD have been observed in men (29–31), and higher rates of mood disorders (depression, dysthimia, and mania) and anxiety disorders (phobias, panic disorder, and OCD) have been observed in women (29,30,32). Further, higher rates of psychiatric comorbidity were found in white women, compared with black women, but no similar distinction was found among men in this treatment sample (30). Overall rates of psychiatric comorbidity across sexes range from 47% for current (29) and 73% for lifetime (30) comorbidity, with more lifetime comorbid disorders (excluding alcohol dependence) being identified in women. In treatment settings, women are also reported to present higher rates of comorbid PTSD and cocaine dependence than do men (33). No significant sex differences in comorbidity rates are described for drug dependence and generalized anxiety disorder, schizophrenia, and eating disorders (30).
Conversely, rates of substance use disorders in other psychiatric populations are also high. For example, women seeking treatment for bipolar disorder have rates of substance use disorders 4 to 7 times higher than are found in women from the community (34).
Psychiatric comorbidity is also an issue for nonclinical samples. Among offenders driving while intoxicated, for instance, 50% of women and 33% of men have at least 1 psychiatric diagnosis in addition to substance use disorder—mostly PTSD and depression (35).
Summary. Because alcohol use disorders are so prevalent among men, the resulting comorbidity rates are higher for men than for women with other drug use disorders when these diagnoses are included in rates of psychiatric comorbidity. When only disorders apart from substance use are considered, women present higher comorbidity rates than do men, owing to high rates of mood and anxiety disorders (depression, mania, phobias, and PTSD)—rates similar to reported psychiatric comorbidity in alcohol use disorders but including dysthimia, OCD, and panic disorder. Men, in the other hand, present higher rates of APD and ADHD. Diagnoses such as schizophrenia display inconsistent results, with data from the ECA showing higher rates in women.
Primary vs Secondary Distinction
Most secondary or substance-induced symptoms and disorders will subside with abstinence from substances. However, independent or primary disorders are less likely to improve with abstinence only and require specific attention from clinicians (36,37). The distinction between primary and secondary is reflected in the temporal relation between the disorders’ onsets. A causal relation can neither be inferred nor ruled out from the order of onset. In the case of comorbidity with substance use disorders, a psychiatric disorder that has its onset during a prolonged period of abstinence is considered to be an independent disorder requiring integrated management.
Treatment Samples. Studies of sex differences in psychiatric comorbidity show that women who abuse alcohol are more likely than men to have been diagnosed with anxiety and depression prior to the development of the alcohol disorder (38).
Schuckit and colleagues investigated the lifetime prevalence rates for concurrent and independent mood and anxiety disorders in a large sample of alcohol-dependent subjects whose family histories showed high rates of alcoholism and intense rates of inpatient treatment (39,40). Men and women had similar rates of concurrent mood and anxiety disorders, but rates of independent disorders (for example, disorders that began either before the onset of alcohol dependence or persisted during periods of 3 months or more of abstinence) were higher in women than in men. These results are similar to those obtained by Kahler and colleagues. (41).
Compton and colleagues assessed the temporal relation in subjects receiving treatment for drug dependency (mainly, cocaine and opiate addictions) (42). They observed that women were significantly more likely to have primary generalized anxiety disorders than were men (53% vs 19% respectively), but no other sex distinctions were identified.
General Population Samples. Data from the NCS show that important sex differences emerge in the temporal relation: men are more likely to report their alcohol use disorder as primary, and women are more likely to report it as secondary, to the other comorbid diagnosis. When the alcohol use disorder is secondary, men more often report a prior CD and antisocial behaviour, while women more often report prior mood, anxiety, and drug use disorders (8). In particular, when alcohol use disorders are comorbid with major depression, the ECA study shows that the alcohol use disorder diagnosis is primary in 78% of cases overall. Among women, however, depression predates the onset of alcohol use disorders in 66% of cases (1).
Summary. The evidence suggests that higher proportions of comorbid diagnoses are primary in women with alcohol use disorders, while the opposite is true for men (a higher proportion of comorbid diagnoses are secondary to alcohol use disorders in men). More studies of the temporal relation between the onset-age of comorbid diagnoses and the onset-age of other drug use disorders are needed to clarify whether sex differences (and potentially different treatment needs) also exist in these populations.
Prior Psychiatric Disorder as a Risk Factor for the Onset of Alcohol Use Disorders
Longitudinal data from a 2-year follow-up survey suggest that, for men, depression is not a risk factor for heavy drinking (that is, drinking 5 or more drinks at least once monthly) (43). However, women with depression at baseline display a higher risk for heavy drinking 2 years later, compared with women without depression (43). The NCS shows that the OR of later developing an alcohol use disorder is increased in women with prior depression, compared with men with prior depression (OR 2.26 vs OR 0.32, respectively, for alcohol abuse; OR 4.10 vs OR 2.67, respectively, for alcohol dependence) (8).
Data for subjects with problem drinking were taken from the ECA follow-up study and examined for an association between the occurrence of depression in the previous year and increased drinking in the subsequent year. The association was indeed confirmed, but contrary to expectations, it was found to be stronger in men (44,45).
Regarding prior PTSD, the NCS described no sex difference in the risk of later developing an alcohol use disorder. Women with prior PTSD have a higher risk (OR 3.37) of later developing alcohol dependence, compared with women who do not have PTSD (8). In women, substance use is a risk factor for the development of PTSD following violent assault (46). Alternatively, female crime victims with comorbid PTSD (particularly victims of sexual violence) are more likely to have alcohol and drug problems than are female crime victims without PTSD; thus, PTSD mediates the relation between childhood rape and adult alcohol abuse in women (47). This 2-way relation was further clarified by a 2-year longitudinal study conducted among 3006 American women. The results confirmed the notion of an ever-worsening cycle in which substance use increases the risk of subsequent assault, and assault increases risk of substance use (48).
When sex differences emerged in the NCS regarding other psychiatric disorders, the risk that persons with any or multiple prior lifetime psychiatric diagnoses would later develop alcohol use disorders was found to be significantly higher for women than for men. Specifically, the risk of later developing alcohol abuse was higher in women with a history of social phobia, simple phobia, depression, mania, drug abuse or dependence, and antisocial behaviour than in men with these disorders. Similarly, the risk of later developing alcohol dependence was higher in women with a history of agoraphobia, depression, drug abuse or dependence, antisocial behaviour, and APD than in men with these disorders (8).
Summary. Overall, psychiatric comorbidity represents more of a risk for the development of alcohol use disorders among women than among men. Data from the NCS suggest that depression is a greater risk factor for the development of alcohol abuse or dependence in women than in men, while the ECA suggests that, among individuals with problem drinking, depression is a greater risk factor for subsequent increased drinking for men than it is for women. PTSD is also a risk factor for the development of alcohol use disorders in women, and vice versa, particularly when violence is involved.
Clinical Characteristics of Women With Psychiatric Comorbidity
Because comorbidity between alcohol use disorders and depression is highly prevalent, most of the literature has focused on this topic. Studies have shown sex-specific, genetic, and environmental influences (49), suggesting the potential for etiological implications. Men with comorbid depression and alcoholism present for treatment with more severe alcoholism than do men who have never suffered from depression. Conversely, women with comorbid depression and alcoholism present for treatment with less severe symptoms of alcoholism than are found in women who have never had depression. However, they have more severe depressive symptoms, when compared with their male counterparts. This suggests that the severity of the clinical picture in women with comorbid depression and alcoholism is related mainly to the severity of the depressive symptomatology. Further, women entering treatment without a history of depression present alcohol problems as severe as those presented by men (50).
Recently, Kahler and colleagues reported that the independent or primary depression more often diagnosed in women with alcohol use disorders, compared with men having the same diagnosis, is associated with more dysfunctional attitudes toward oneself and with poorer coping behaviours (41). This observation suggests that such individuals may be particularly vulnerable to recurrent depression.
Compared with substance abusers who do not have comorbid diagnoses, women with comorbid substance abuse and anxiety disorders present a different personality profile, with lower thrill- and adventure-seeking traits in contrast to their male counterparts (51).
Among persons being treated for cocaine dependence, women represent 48% of those patients diagnosed with comorbid depression, whereas they represent 25% of patients without a diagnosis of depression. These groups have significantly distinct characteristics, with overall worse functioning among patients suffering from comorbid depression and cocaine dependence (52).
An exploratory study among inpatients of a residential program found no significant demographic differences between women and men with comorbid substance use and psychiatric disorders; however, women were more likely to have drug problems in addition to alcohol problems, to have overdosed on drugs, and to report maternal relatives with alcohol and drug problems. Also, women were more troubled by social and family problems requiring counselling and presented for treatment with higher psychiatric severity than did men (53).
Some studies (54,55), but not all (53), have also described more severe medical problems in women with comorbid substance use and other psychiatric diagnoses than in men with these diagnoses.
Women with substance use disorders combine 2 important risk factors for both suicidal ideation and suicide attempt, the risk being 1.7 to 2.2 times higher in women than in men and 3.9 to 5.8 times higher in persons with substance use disorders than in those without such a history. Psychiatric comorbidity poses additional risk for suicidal behaviour in women with multiple comorbidity (56). Clinical studies also show that women with substance dependence report suicide attempts more often than do men with the same diagnosis (57).
Summary. Psychiatric comorbidity is associated with distinct clinical presentations according to sex (particularly in terms of each disorder’s severity), of overall functioning, and of suicide risk profiles. The severity of the clinical picture in alcohol use disorders is to a greater extent owing to depression in women with comorbidity and to a greater extent owing to the alcohol disorder in men with comorbidity.
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