Download - Comorbidity of Depression and Substance Abuse Disorders- Risk Factors, Effects, and Treatment
Comorbidity of Depression and Substance Abuse Disorders 1
Comorbidity of Depression and Substance Abuse Disorders: Risk Factors, Effects, and
Treatment
Sarah Castillo
Quinnipiac University
Author Note
Sarah Castillo, Psychology Department
Quinnipiac University
Correspondence concerning this article should be addressed to:
307 Washington Drive, Ramsey, NJ, 07446
Comorbidity of Depression and Substance Abuse Disorders 2
Abstract
The comorbidity of depression and drug addiction is not fully understood yet it is
becoming clear that the co-occurring disorders are highly prevalent, thus it is crucial that the
relationship between the two be studied in depth. This study examined the relationship of the two
disorders, factors that may contribute to the co-occurring disorder, and possible therapies to gain
insight on the most effective treatment options. The development of the depression and
addiction, diagnosis issues, possible predictors, neurological mechanisms, and several treatment
types are discussed. A proposed study using a controlled experiment is given to add more
empirical support for combination therapies.
Comorbidity of Depression and Substance Abuse Disorders 3
Table of Contents
Chapter 1: Addiction and Depression………………………………………………………….6
Depression and Diagnostic Criteria…………………………………………………....6
Addiction and Diagnostic Criteria………………………………………………………9
Development of Comorbidity…………………………………………………………..11
Conclusion………………………………………………………………………………14
Chapter 2: Difficulty of Diagnosis ……………………………………………………………..15
Inconsistent Patient Assessment………………………………………………………...15
Inaccurate Patient Self-Reports…………………………………………………………16
Conclusion ……………………………………………………………………………...18
Chapter 3: Epidemiology………………………………………………………………......……18
Genetic Factors………………………………………………………………………….19
Gender…………………………………………………………………………..19
Ethnicity………………………………………………………………………………....20
Environmental Factors…………………………………………………………………..21
Socioeconomic Status…………………………………………………………...22
Criminal History………………………………………………………………...22
Conclusion………………………………………………………………………………23
Comorbidity of Depression and Substance Abuse Disorders 4
Chapter 4: Neurology…………………………………………………………………………24
Kappa Opioid Receptors and Dynorphin……………………………………………..24
Kappa Opioid Receptor Sex Differences…………………………………………..…25
Kappa Opioid Receptors and Serotonin………………………………………………26
Conclusion………………………………………………………………………….…27
Chapter 5: Treatment……………………………………………………………………….…28
Twelve-Step Facilitative Therapy and Cognitive Behavioral Therapy…………….…28
Integrated Cognitive Behavioral Therapy versus Twelve-Step Program……….…….29
Medication…………………………………………………………………………….30
SSRI…………………………………………………………………………...30
SSRI and Opioid Receptor Antagonist………………………………………..32
Combination Therapy………………………………………………………………….33
Conclusion……………………………………………………………………………..34
Chapter 6: Research Proposal………………………………………………………………….35
Method…………………………………………………………………………………36
Participants…………………………………………………………………………….36
Materials……………………………………………………………………….36
Comorbidity of Depression and Substance Abuse Disorders 5
Measures………………………………………………………………36
Medications……………………………………………………………36
Procedure………………………………………………………………………36
Expected Results………………………………………………………………………37
Discussion……………………………………………………………………………..38
Predictions……………………………………………………………………..38
Limitations……………………………………………………………………..38
Overall Conclusion……………………………………………………………………..38
References………………………………………………………………………………………41
Appendix A- Annotated Bibliography…………………………………………………………48
Appendix B- Review Paper on Three Experts…………………………………………………76
Comorbidity of Depression and Substance Abuse Disorders 6
Chapter 1: Depression and Substance Addiction
Depression and drug addiction occur together in a large percentage of people. Twenty
percent of people with either disorder are suffering from the other disorder as well, and this
number is steadily rising. (Brauser, 2010). Due to the high percentage of comorbidity of
depression and drug addiction, it is crucial that the relationship between the two be studied in
depth.
Depression and Diagnostic Criteria
There are several types of depressive disorders including persistent depressive disorder,
in which a person experiences a mild or moderate depressed mood lasting at least two years and
may experience periods of more severe symptoms, and major depression in which a person
experiences severe symptoms that may interfere with daily activities such as eating, sleeping, or
working (NIMH). Signs and symptoms of depression vary depending on the particular disorder,
however, general signs and symptoms include persistent sad, anxious, and/or hopeless feelings,
feelings of unimportance or weakness, irritability, anhedonia, change in sleep, energy, and/or
appetite, distractedness, indecisiveness, and thoughts of suicide (NIMH). Diagnostic criteria for
an unspecified depression disorder as given by the Diagnostic and Statistical Manual of Mental
Disorders (DSM) was used for all research that will be discussed though various editions may
have been used. Much of the diagnostic criteria for an unspecified depression disorder from
DSM-V are as follows:
This category applies to presentations in which symptoms characteristic of a depressive
disorder that cause clinically significant distress or impairment in social, occupational, or other
Comorbidity of Depression and Substance Abuse Disorders 7
important areas of functioning predominate but do not meet the full criteria for any of the
disorders in the depressive disorders diagnostic class. The unspecified depressive disorder
category is used in situations in which the clinician chooses not to specify the reason that the
criteria are not met for a specific depressive disorder, and includes presentations for which there
is insufficient information to make a more specific diagnosis (e.g., in emergency room settings).
Specify if:
With anxious distress: Anxious distress is defined as the presence of at least two of the
following symptoms during the majority of days of a major depressive episode or persistent
depressive disorder (dysthymia):
1. Feeling keyed up or tense.
2. Feeling unusually restless.
3. Difficulty concentrating because of worry.
4. Fear that something awful may happen.
5. Feeling that the individual might lose control of himself or herself.
o With melancholic features:
G. One of the following is present during the most severe period of the current episode:
1. Loss of pleasure in all, or almost all, activities.
2. Lack of reactivity to usually pleasurable stimuli (does not feel much better, even
temporarily, when something good happens).
H. Three (or more) of the following:
1. A distinct quality of depressed mood characterized by profound despondency, despair,
and/or moroseness or by so-called empty mood.
2. Depression that is regularly worse in the morning.
Comorbidity of Depression and Substance Abuse Disorders 8
3. Early-morning awakening (i.e., at least 2 hours before usual awakening).
4. Marked psychomotor agitation or retardation.
5. Significant anorexia or weight loss.
6. Excessive or inappropriate guilt.
o With atypical features: This specifier can be applied when these features predominate during
the majority of days of the current or most recent major depressive episode or persistent
depressive disorder.
J. Mood reactivity (i.e., mood brightens in response to actual or potential positive events).
K. Two (or more) of the following:
1. Significant weight gain or increase in appetite.
2. Hypersomnia.
3. Leaden paralysis (i.e., heavy, leaden feelings in arms or legs).
4. A long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of
mood disturbance) that results in significant social or occupational impairment.
L. Criteria are not met for “with melancholic features” or “with catatonia” during the same
episode.
o With psychotic features: Delusions and/or hallucinations are present.
o With mood-congruent psychotic features
o With mood-incongruent psychotic features
o With catatonia: The catatonia specifier can apply to an episode of depression if catatonic
features are present during most of the episode. See criteria for catatonia associated with a
mental disorder (for a description of catatonia, see the chapter “Schizophrenia Spectrum and
Other Psychotic Disorders”).
Comorbidity of Depression and Substance Abuse Disorders 9
o With peripartum onset
o With seasonal pattern
o Specify current severity:
Severity is based on the number of criterion symptoms, the severity of those symptoms, and the
degree of functional disability.
Mild: Few, if any, symptoms in excess of those required to make the diagnosis are present,
the intensity of the symptoms is distressing but manageable, and the symptoms result in minor
impairment in social or occupational functioning.
Moderate: The number of symptoms, intensity of symptoms, and/or functional impairment
are between those specified for “mild” and “severe.”
Severe: The number of symptoms is substantially in excess of that required to make the
diagnosis, the intensity of the symptoms is seriously distressing and unmanageable, and the
symptoms markedly interfere with social and occupational functioning (5th ed.; DSM–5;
American Psychiatric Association, 2013).
It is believed that depression is a result of a combination of factors involving genetics and
environment with psychological, biological, and societal influences (NIMH) and risk factors
(such as gender or ethnicity) and/or predictors which have been identified to aid in the diagnosis
of depression. Current available treatments for depression include medications such as
antidepressants and herbal supplements, cognitive-behavioral therapy, interpersonal therapy, and
brain stimulation therapies (NIMH).
Addiction and Diagnostic Criteria
Substance addiction may be defined as a continuing, relapsing disorder characterized by
dependence of the substance, impairment, compulsive substance seeking and use despite harmful
Comorbidity of Depression and Substance Abuse Disorders 10
consequences that may occur and additional symptoms may include the following:
neurochemical changes in the brain, development of tolerance to the substance, occurrence of
withdrawal symptoms, and decrease or cessation of usual activities because of substance use
(NIDA, 2012). Treatment for substance abuse includes medications or behavioral therapy
(NIDA, 2012). Much of the diagnostic criteria for an unspecified addiction disorder from DSM-V
are as follows:
A. A problematic pattern of use of an intoxicating substance not able to be classified
within the alcohol; caffeine; cannabis; hallucinogen (phencyclidine and others); inhalant;
opioid; sedative, hypnotic, or anxiolytic; stimulant; or tobacco categories and leading to
clinically significant impairment or distress, as manifested by at least two of the following,
occurring within a 12-month period:
The substance is often taken in larger amounts or over a longer period than was
intended.
There is a persistent desire or unsuccessful efforts to cut down or control use of the
substance.
A great deal of time is spent in activities necessary to obtain the substance, use the
substance, or recover from its effects.
Craving, or a strong desire or urge to use the substance.
Recurrent use of the substance resulting in a failure to fulfill major role obligations at
work, school, or home.
Continued use of the substance despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of its use.
Comorbidity of Depression and Substance Abuse Disorders 11
Important social, occupational, or recreational activities are given up or reduced
because of use of the substance.
Recurrent use of the substance in situations in which it is physically hazardous.
Use of the substance is continued despite knowledge of having a persistent or recurrent
physical or psychological problem that is likely to have been caused or exacerbated by
the substance.
Tolerance, as defined by either of the following:
a. A need for markedly increased amounts of the substance to achieve intoxication or
desired effect.
b. A markedly diminished effect with continued use of the same amount of the
substance.
Withdrawal, as manifested by either of the following:
a. The characteristic withdrawal syndrome for other (or unknown) substance (refer to
Criteria A and B of the criteria sets for other [or unknown] substance withdrawal,
p. 583).
b. The substance (or a closely related substance) is taken to relieve or avoid withdrawal
symptoms.
Specify current severity:
Mild: Presence of 2–3 symptoms.
Moderate: Presence of 4–5 symptoms.
Severe: Presence of 6 or more symptoms (5th ed.; DSM–5; American Psychiatric
Association, 2013).
Development of Comorbidity
Comorbidity of Depression and Substance Abuse Disorders 12
There are many potential origins of the co-occurring disorders (COD). One possible
explanation for the development of COD stems from people who suffer from depression who
attempt to self-medicate or alleviate their symptoms by using drugs or other substances which
they later become addicted to (Crum et al., 2013; Worley, Trim, Tate, Hall, & Brown, 2010).
Crum and colleagues (2013) aimed to determine whether or not alcohol self-medication of mood
symptoms, including depressive symptoms, would increase the probability of alcohol
dependence. The researchers drew a sample from a study done by the National Institute on
Alcohol Abuse and Alcoholism (Crum et al., 2013). They found results that suggest drinking to
alleviate or self-medicate mood symptoms was associated with future dependence disorders,
particularly in participants with depression symptoms (Crum et al., 2013). This possible
explanation for the development of comorbidity may be supported with another study done by
Worley, Trim, Tate, Hall, and Brown (2010) who investigated factors affecting treatment service
utilization as well as correlational characteristics of those with comorbid depression and
substance abuse disorders that may affect treatment. They found that more severe baseline
depressive symptoms were related to longer inpatient admissions for treatment (Worley et al.,
2010), suggesting that those with greater depressive symptoms may also have had greater
substance abuse symptoms or needed additional therapy to achieve abstinence. Although there
could be multiple explanations for this finding, one possibility that would be in line with the
findings of Crum and colleagues (2013) is that those with severe depression struggled to achieve
abstinence due to the desires or tendencies to self-medicate their depressive symptoms. Findings
from both of these studies may be indicative of an increased challenge when managing substance
abuse disorders due to depression.
Comorbidity of Depression and Substance Abuse Disorders 13
Oppositely, substance abuse and addiction can cause depression through use of the drug
itself, as a withdrawal symptom, or due to brain changes caused by the drug which will be
elaborated on later in this paper. This may increase the risk for depression or may worsen already
existing mental health problems by triggering depressive symptoms (Langas, Malt, &
Opjordsmoen, 2013; Worley et al., 2010). An alternative explanation for the finding of severe
baseline depressive symptoms correlating to longer inpatient admissions for treatment in the
Worley study (Worley et al., 2010) could also be that participants needed more intensive
treatment or struggled to reach abstinence due to severe substance abuse disorders which then
cause severe depressive symptoms. This explanation would be in line with the findings of a later
study done by Langas, Malt, and Opjordsmoen (2013) who studied substance abuse disorders
including substance-induced major depressive disorders and independent co-occurring substance
use disorders and major depressive disorders. They assessed patients from a hospital with no
history of prior addiction or psychiatric treatment who were admitted to treatment within 18
months and were referred to the study (Langas et al., 2013). These researchers assessed
participant disorder severity using the Alcohol Use Disorder Identification Test (AUDIT), Drug
Use Disorder Identification Test (DUDIT), Psychiatric Research Interview for Substance and
Mental Disorders (PRISM), and the Structured Clinical Interview for DSM-IV, Axis-II,
Personality Disorders (SCID-II) (Langas et al., 2013). They found that some participants with
comorbid depression and substance abuse disorders experienced decreased depressive symptoms
during substance abstinence and believed that this was indicative of a subgroup of participants
with co-occurring disorders who experienced depressive symptoms as a result of substance use
(Langas et al., 2013). Furthermore, researchers believed that results suggested that the risk of
Comorbidity of Depression and Substance Abuse Disorders 14
developing depression or depressive symptoms could increase over time during long-term
substance abuse (Langas et al., 2013).
Suter, Strik, and Moggi (2011) sought to determine the association between MDD
diagnosis and/or “clinically significant depressive symptoms” and AUD. They examined patients
with SUD, focusing on those with AUD, who entered a participating residential treatment
program and assessed them upon admission to the program, release, and after a one year follow-
up (Suter, Strik, & Moggi, 2011). The researchers looked at abstinence from use, first time
alcohol use after program, severity of dependence, consequence from use, use during stay,
depressive symptoms, and prior treatments for SUD or psychiatric disorders (Suter et al., 2011).
Patients with comorbid AUD and depressive symptoms used more psychiatric treatments by the
follow-up and there was no significant difference for time to drink (Suter et al., 2011).
Associations between MDD and relapse were found as were associations between depressive
symptoms and severity of dependence (Suter et al., 2011). Ultimately the researchers concluded
that the comorbidity related to a higher risk of drinking for those with AUD (Suter et al., 2011).
The final explanation for the co-occurring disorders (COD) would be these disorders
developing simultaneously. Marshall and colleagues (2012) designed a study to analyze alcohol
abuse, depression, and Post-traumatic stress disorder (PTSD) in those who served in the National
Guard during and after deployment. The researchers found a high rate of both alcohol abuse and
depressive symptoms during and after deployment in participants with no previous history of
either disorder and concluded that there may be environmental risk factors, such as stressful
situations, that both disorders have in common (Marshall et al., 2012).
Conclusion
Comorbidity of Depression and Substance Abuse Disorders 15
The purpose of this study is to examine the relationship of comorbid depression and
substance addiction, factors that may contribute to the co-occurring disorder, and possible
therapies to gain insight on the most effective treatment options. Because depression and
substance abuse disorders are prevalent in our society and the rate of them co-occurring in the
population is rising (Brauser, 2010), it is imperative to gain a better understanding of their
relationship including what they have in common and why they may occur together. As
previously mentioned, there are several possibilities for how they may develop together
including depression leading to self-medication through substances, depression caused by
substances used, or the disorders developing at the same time. Chapter two of this paper will
examine issues with diagnoses including health care provider error and inaccurate patient report.
The main components of chapter three are predictors of comorbidity and factors that may
increase the likeliness of its development. Chapter four will be dedicated to the neurological
processes that contribute with depression and substance abuse. Chapter five discusses previous
research on treatment options including twelve-step facilitation (TSF) programs and cognitive
behavioral therapy (CBT). Finally, chapter six proposes a new study based off of previous
research done for combination behavioral and pharmacological therapies.
Chapter 2: Difficulties of Diagnosis
Although depression and substance addiction are two common and easily recognizable
disorders, recognizing them as occurring together can sometimes be complex. Diagnosing
patients with comorbid depression and addiction may be particularly challenging for a host of
reasons. Challenges for diagnosis include unclear diagnostic criteria for COD and/or lack of
practitioner training, attributing a patient’s symptoms to one disorder or another (as opposed to
Comorbidity of Depression and Substance Abuse Disorders 16
recognizing dual existing disorders), or the patient only recognizing or identifying with one
disorder.
Inconsistent Patient Assessment
In a study done by Darghouth, Nakash, Miller, and Alegria (2012) that focused on the
assessment of those with COD, the researchers found interactions between patients and treatment
providers at eight mental health clinics. The researchers categorized patients diagnosed and
admitted treatment into four groups: those diagnosed with depressive disorders, with a substance
abuse disorder, with both disorders (COD), or with neither disorder (Darghouth, Nakash, Miller,
& Alegria, 2012). They found that during the intake interview where practitioners assess and
diagnose patients, the amount that many symptoms such as depressed feelings or substance use
were discussed or brought up varied greatly between groups (Darghouth et al., 2012). They also
found that practitioners failed to discuss some symptoms related to depression or substance
abuse at all in some interviews (Darghouth et al., 2012) which suggests a lack of standardization
when providing diagnoses and supports a previous study done by Chen and colleagues (2011)
who found that only 42% of substance abuse disorder treatment facilities used mental health
screenings. Researchers also found that ethnicity of either the healthcare provider or the patient
skewed diagnoses, there were inconsistencies in information exchange between providers, and
providers sometimes used heuristics to diagnose a patient as opposed to adhering to diagnostic
criteria (Darghouth et al., 2012). Some people may regard symptoms as indications of one
disorder, particularly with those who were identified as addicts. Some people also do not think
they have a certain problem so they never seek the appropriate treatment
Inaccurate Patient Self-Reports
Comorbidity of Depression and Substance Abuse Disorders 17
Another prominent issue in providing a correct diagnosis for COD lies within the
patient’s failure to recognize a dual existing disorder. Researchers found that patients also
sometimes attribute their symptoms to either depression or substance addiction instead of
recognizing that they suffer from both (Chan, Huang, Bradley, & Unitzer, 2014; Mojtabai, Chen,
Kaufmann, & Crum, 2014). Chan and colleagues (2014) studied treatment programs for
substance use disorders and the treatment’s effects on depressive symptoms by examining data
from their previous study on the Mental Health Integration Program (MHIP), a state program
(Chan et al., 2014). They used the Patient Health Questionnaire-9 (PHQ-9) to measure
depressive symptoms and the GAIN-SS for indications of drug abuse severity of the participants
of MHIP (Chan et al., 2014). Through patient interviews, they found evidence regarding the
inability of depressed patients to recognize their need for addiction treatment and suggested that
it may have been the depression itself that caused the lack of perceived need. Mojtabai and
colleagues had similar findings (2014) when they analyzed a seven-year, cross-sectional study to
determine potential barriers that people with mental health issues and/or substance abuse
disorders when searching for treatment options. This group of researchers found that many
participants either attributed symptoms to only one disorder if they were not diagnosed with a
co-occurring disorder or did not feel that they needed treatment for particular symptoms. For
example, a patient diagnosed with a substance abuse disorder may attribute feelings of
depression to the substance use instead of recognizing the depression as a separate disorder and
may feel that it is unnecessary to seek treatment for depression because they have been
diagnosed or because their symptoms are “not that bad”. Inability of the patient to recognize a
dual disorder presents issues in diagnosis when diagnosis relies partly on patients accurately
reporting symptoms.
Comorbidity of Depression and Substance Abuse Disorders 18
There has also been evidence that shows some people with comorbid depression and
addiction may not report having COD or may not disclose all of their symptoms (Mericle, Park,
Holck, & Arria, 2012; Mojtabai et al., 2014). In the same study done by Mojtabai, Chen,
Kaufmann, and Crum (2014), participants were found to resist seeking treatment for their
disorders or certain symptoms. Their findings are consistent with an earlier study by Mericle,
Park, Holck, and Arria (2012) when they sought to look into possible correlations between
people with co-occurring disorders using data from three national surveys as well as a study done
by Chen and colleagues (2011) who studied people entering treatment programs that were
diagnosed with COD using the DSM-IV in order to learn about how substance use, gender, and
treatment type affected treatment outcome. In all three studies, reasons for patients not reporting
their condition included fear of stigma and/or shame as well as fear of consequences from
reporting, such as hospitalization (Mericle et al., 2012; Chen et al., 2013; Mojtabai et al., 2014)
while the study done by Chen and colleagues specified that men are less likely to be diagnosed
with COD.
Conclusion
In this chapter, errors with diagnosis of comorbid depressive and substance abuse
disorders were discussed. Errors in diagnosis may stem from variation in patient assessment
across practitioners (Darghouth et al., 2012), attribution of patient symptoms to either depression
or substance addiction instead of recognizing that they suffer from both (Chan, Huang, Bradley,
& Unitzer, 2014; Mojtabai, Chen, Kaufmann, & Crum, 2014), and/or inaccurate self-reports by
the patient due to feelings of shame or fear (Mericle et al., 2012; Chen et al., 2013; Mojtabai et
al., 2014).More works needs to be done to eliminate these errors in patient diagnosis; without
accurately assessing people and establishing who suffers from comorbid disorders, it is not
Comorbidity of Depression and Substance Abuse Disorders 19
possible to correctly examine the comorbidity of the two disorders and it is not possible to
accurately treat those who suffer from them.
Chapter 3: Epidemiology
While diagnosing co-occurring depression and substance abuse disorders have been
shown to be challenging, examining epidemiology and common factors of those who have been
accurately diagnosed to establish predictors may prove valuable in improving both diagnosis and
treatment practices in the future. Many researchers have already begun to find characteristics that
may serve as predictors or place people more at risk for the co-occurring disorders.
Genetic Factors
Results from human and animal studies have been found that suggests genetics play a
large role in substance abuse and depression disorders however, specific genes related to drug
addiction and/or depression have not been identified (Lydecker et al., 2010; Chartoff et al.,
2012). However, certain genetic factors such as gender and age of onset have been shown to
affect the progression of the disorders.
Gender. Studies have shown that both genders develop similar levels of addiction
severity (Brown, Bennett, & Bellack, 2011). In a study done by Brown, Bennett, and Bellack
(2011) that focused on predictors of substance abuse treatment outcome in those with COD,
participants were diagnosed using criteria from DSM-IV and were randomly assigned to one of
two treatment programs (Brown et al., 2011). They found that both men and women with the
comorbid disorders had similar substance abuse severity; however men reported less desire to
undergo treatment (Brown et al., 2011) which may account for Chen and colleague’s findings
that men are less likely to be diagnosed with co-occurring disorders (Chen et al., 2013).
Comorbidity of Depression and Substance Abuse Disorders 20
Although addiction severity does not differ between genders, there is an overwhelming
amount of evidence that states women are more likely to suffer from depression (Langas, et al.,
2013; Russell et al., 2014). Two recent studies examined participants in the Minnesota Twin
Family Study to study longitudinal associations between major depressive disorders and drug
and alcohol dependence and found that women who develop depressive symptoms at a young
age are at an especially high risk for developing a co-occurring substance abuse disorder at an
older age (Marmorstein, 2010; Marmorstein, Iacono, & Malone, 2010). However, one of the
researchers did find that the correlation of major depressive symptoms leading to a COD with
substance abuse was weakened when age of onset depressive symptoms increased (Marmorstein,
2010). The opposite is also true, that is, young females who experience substance abuse at a
young age are at an increased risk for developing depressive symptoms (Marmorstein, 2010;
Marmorstein, et al., 2010).
Chen and colleagues (2013) used public information from the National Survey on Drug
Use and Health including all participants who were above 18 and met requirements for major
depressive episodes and assessed them using the DSM-IV, the Sheehan Disability Scale,
interviews, and questionnaires in order to determine whether or not those with comorbid
disorders used different types of mental health services or different amounts and whether or not
they had a greater perceived unmet need for treatment. While other studies found that women are
more likely to suffer from depression alone (Langas, et al., 2013; Russell et al., 2014), and both
genders have similar addiction severities (Brown, Bennett, & Bellack, 2011), these researchers
made the distinction that men are more likely to suffer from comorbid depression and substance
abuse (Chen et al., 2013). While the correlation of early onset of major depressive symptoms and
the development of COD was not as strong in males as in females in the Marmorstein study, the
Comorbidity of Depression and Substance Abuse Disorders 21
correlation is still there (Marmorstein et al., 2010), suggesting that although COD is more
prominent in men, age is not as important a factor for males as for females. Furthermore, the
studies done by Brown and colleagues (2011) and Chen and colleagues (2013) also showed
correlations suggesting that men who are single (never married, divorced, separated, or
widowed) were at a higher risk for the development of COD although possible explanations for
the correlation was never mentioned.
Ethnicity
In addition to gender, major differences in COD occurrence have been found to vary
across ethnic groups, although it is unclear whether or not this is due to genetic or environmental
factors (Green, Zebrak, Fothergill, Robertson, & Ensminger, 2012). Most studies obtained
results that suggested African Americans are more likely to suffer from co-occurring depression
and drug abuse (Chen et al., 2013; Green et al., 2012). A study done by Green and colleagues
(2012) that used data from the Woodlawn Study to examine the comorbidity between depression
and substance abuse disorders found that within the African American cohort there was a high
prevalence of COD while the study done later by Chen and colleagues (2013), who used national
data on a more representative population, yielded similar findings. However, it is important to
note that one study conducted by Mericle, Park, Holck, and Arria (2012) yielded results that
proposed Caucasians were more prone to the development of COD. Although these results
contradict those of other studies, these researchers also found that certain ethnic groups,
including African Americans, may be less likely to report psychiatric illnesses, a finding that is
consistent with other studies and which may account for their inconsistent data (Mericle, et al.,
2012).
Environmental Factors
Comorbidity of Depression and Substance Abuse Disorders 22
Not only can genetic factors affect one’s susceptibility for the development of depression
and/or addiction but environmental factors can play a role as well. Studies have found that
prolonged stress can lead to an increased chance in developing the disorders due to emotional
factors and /or behavioral responses as well as neurological changes occurring in the brain
(Bruchas et al., 2011; Russell et al., 2014). Other environmental factors such as socioeconomic
status and criminal history have also been found to play a role; however, it may be possible that
their effects on the development of the disorders may be due to their association with prolonged
stress (Jaffe et al., 2012)
Socioeconomic Status. There is a vast amount of evidence pointing to socioeconomic
status factors such as income, employment status, and education, as indicators and/or predictors
of comorbid depression and substance abuse disorders. Multiple studies have found a correlation
between low incomes (less than $20,000) and the development of COD (Chen et al., 2013; Green
et al., 2012). Because low income also affects access to treatment, as will be discussed in later
segments of this paper, income may also play a role in severity of COD.
Additional studies have also found that unemployment is a large risk factor for the
development of co-occurring depression and addiction (Jaffe, Du, Huang, & Hser, 2012; Chen et
al., 2013). A study conducted by Jaffe, Du, Huang, and Hser (2012) focused on drug-abusing
offenders with comorbid psychiatric disorders used data from the California Alcohol and Drug
Data System and measured addiction severity using the Addiction Severity Index (ASI) and
mental health using criteria from the Department of Mental Health (DMH). Their results not only
found unemployment to be a risk factor for COD, but also showed a connection between
unemployment and increased severity of the depressive symptoms participants experienced
(Jaffe et al., 2012).
Comorbidity of Depression and Substance Abuse Disorders 23
While income levels and employment status are great risk factors for COD, education
level has also shown to be a valid predictor of future disorder development. Langas and
colleagues (2013) found that those who had lower education were more likely to suffer from
COD, particularly major depression stemming from substance abuse. Other studies have also
made similar conclusions (Chen et al., 2013; Green et al., 2012).
Criminal History. Some studies have also found that criminal record may be related to
comorbid depression and addiction (Brown et al., 2011; Jaffe et al., 2012). Brown and
colleagues (2011) suggested that recent arrests had a particular correlation to addiction and
participation in treatment. Jaffe, Du, Huang, and Hser (2012) found that recent arrests and
reoffenses of crimes were indicators and/or predictors of COD.
Furthermore, results from the study done by Marmorstein (2010) showed that comorbid
depression and delinquent behavior in adolescents was a prominent indicator for future COD
particularly in young females. She also found gender differences in the accuracy of depression
and delinquent being a predictor for comorbid depression and addiction, stating that in females,
this correlation lessens with age, that is, as females get older, depression and delinquent behavior
becomes a less accurate predictor of COD (Marmorstein, 2010). However, in males, the
correlation of depression and delinquent behavior predicting future COD is lower, but not age
dependent; the correlational strength stays roughly the same throughout ages (Marmorstein,
2010).
Conclusion
Many characteristics have been identified as potential risk factors for developing
comorbid depressive and substance abuse disorders. Although no gene related to depression and
addiction has been identified, it is believed by many that genetic factors play a large role in the
Comorbidity of Depression and Substance Abuse Disorders 24
development of the disorders due to positive correlations of family history, gender, and
developmental changes that occur at early onset (i.e. adolescence), of either of the disorders
(Lydecker et al., 2010; Marmorstein, 2010; Marmorstein, et al., 2010; Brown et al., 2011;
Chartoff et al., 2012; Chen et al., 2013). Environmental factors have also been established.
Results from several studies have shown that socioeconomic status factors such as low income,
low education, and unemployment are associated with the development of depressive disorders
and substance abuse as is prolonged stress and criminal history (Bruchas et al., 2011; Green et
al., 2012; Jaffe et al., 2012l Chen et al., 2013;Langas et al., 2013; Russell et al., 2014). There
have also been numerous studies that determined that ethnicity may be a factor in the co-
occurring disorders, stating that African Americans had the highest risk (Chen et al., 2013; Green
et al., 2012), although the reason for this correlation has not been determined. Through finding
these possible predictors of depression and substance abuse, it may be easier to understand the
relationship between the disorders as well as how to modify diagnosis treatment to make them
more successful.
Chapter 4: Neurology
As previously stated, drug use can cause physiological brain changes that may lead to
depression. Furthermore, depression can also cause brain changes. This is because both
conditions cause alterations in certain neurochemical mechanisms (Bruchas et al, 2011; Konova,
Moeller, & Goldstein, 2013). Studies have found that prolonged stress can lead to psychological
disorders such as depression and increased likelihood of drug abuse not only because of
emotional factors and /or behavioral responses, but also because of neurological changes
occurring in the brain (Bruchas et al., 2011; Russell et al., 2014). Researchers have found
Comorbidity of Depression and Substance Abuse Disorders 25
evidence that some of these neurological changes may be a result of the release of peptide called
dynorphin as a biological stress response (Bruchas et al., 2011).
Kappa Opioid Receptors and Dynorphin
Dynorphin, an endogenous ligand found at kappa opioid receptors (KORs) and that
activate KORs, produces depressive-like effects and contributes to addictive behavior (Russell et
al., 2014). More specifically, certain neurological pathways for dynorphin are believed to play a
significant role in drug seeking (addictive) behaviors, withdrawal symptoms such as cravings
and depression, and relapse (Bruchas et al., 2011).
Chartoff and colleagues (2012) examined the role of KORs in behavioral signs of drug
withdrawal by implanting intracranial self-stimulation electrodes into male Sprague-Dawley rats
and administering cocaine and/or norbinaltorphimine (norBNI), a KOR antagonist, to some
through intracerebroventricular (ICV) before conducted a forced swim test to evaluate changes in
behavior and viewing brain histology (Chartoff et al., 2012). They found that while KORs
typically produce depressive behaviors in drug users, administration of a KOR antagonist
weakened cocaine-induced behaviors, concluding that KOR antagonists could be effective if
given as treatment before a stress occurs (Chartoff et al., 2012).
Kappa Opioid Receptor Sex Differences
Researchers have also found sex differences in KOR expression (Wang et al., 2011;
Russell et al., 2014). Wang and colleagues (2011) examined sex differences in guinea pigs due to
their similar KOR distribution of human and gave them U50,488H, a KOR agonist, as well as
[3H]U69,593 and U50,488H-stimulated guanosine (Wang et al., 2011). The guinea pigs were
then monitored and videotaped, while researchers examined abnormal posture, immobility,
antinociception (tested through paw pressure), and inhibition of cocaine-induced hyperactivity as
Comorbidity of Depression and Substance Abuse Disorders 26
well as examined brain slices and estrous cycles were monitored in females (Wang et al., 2011).
The researchers found that U50,488H resulted in more significant changes in posturing and paw
pressure in male guinea pigs and reduced cocaine-induced hyperactivity more significantly in
females (Wang et al., 2011). Furthermore, [3H]U69,593 and U50,488H-stimulated guanosine
bound more in males everywhere in the brain except for the dentate gyrus, where females
experienced greater binding (Wang et al., 2011). These findings were determined to be
representative of a sex-dependent difference in KOR activation and/or sensitivity in specific
parts of the brain which consequently affects function (Wang et al., 2011) and were later
supported by the results of Russell and colleagues (2014).
Russell and colleagues (2014) completed intraperitoneal injections and intracranial self-
stimulation on sexually mature rats and analyzed data using liquid chromatography, mass
spectrometry of blood samples, and examination corticotropin-releasing factor (CRF) in the
paraventricular nucleus (PVN) to measure possible effects of U-50488, a KOR agonist (Russell
et al., 2014). Corresponding to the results of Wang and colleagues (2011),these researchers
found that females are less sensitive than males to the depressive-like effects dynorphin, and
theorize that this may be because estrogen offsets the inhibitory effects of KORs on dopamine
release (Russell et al., 2014). The researchers suggest that KORs play a bigger part in drug- and
stress-induced depressive-like states in males (Russell et al., 2014); and their conclusions of
existing sex differences in sensitivity to the agonist, with the conclusions of Wang and
colleagues (2011), may contribute to the sex differences in comorbid depression and addiction as
discussed in Chapter Three.
Kappa Opioid Receptors and Serotonin
Comorbidity of Depression and Substance Abuse Disorders 27
An experiment done by Bruchas and colleagues (2011) used mice that were specifically
bred to either exhibit or eliminate certain genotypes related to mitogen-activated protein kinases
(MAPK), a protein kinase often activated by the dynorphin/KOR system during stress, and used
conditioned place aversion, intracranial injection, gave the mice cocaine and reinstated them and
observed for stress-induced social avoidance as well as other behaviors. They found that one
particular isoform of MAPK, p38 MAPK, played a significant role in serotonin transport during
stress-induced behavioral responses of the mice and is believed to play a role in increasing
serotonin reuptake (Bruchas et al., 2011) which supports the hypothesis that MAPK plays a role
in stress-induced mood changes and may play a role in addiction and depression through its
effects on serotonin.
The role of serotonin and dynorphin in depression and addiction was also investigated in
an earlier experiment done by Chartoff and other researchers (2009), where the researchers
hypothesized that cAMP response element binding protein (CREB) in the nucleus accumbens
(NAc) contributed to depressive symptoms and that desipramine (DMI), a tricyclic
antidepressant that inhibits norepinephrine reuptake, and to a lesser extent serotonin, would
inhibit dynorphin activation and CREB in the NAc. In this study, pregnant rats were given either
DMI or fluoxetine, a selective serotonin reuptake inhibitor (SSRI), and cell culture studies were
performed while male rats that were given the drugs and performed behavioral test (Chartoff et
al., 2009). The researchers confirmed their hypothesis; increased CREB function in the NAc was
positively correlated with increased depressive symptoms and DMI successfully decreased
CREB function as well as depressive symptoms through dynorphin inhibition (Chartoff et al.,
2009). The researchers also believed that dynorphin played a significant role in behavioral
Comorbidity of Depression and Substance Abuse Disorders 28
changes in the rats due to KORs in the NAc (Chartoff et al., 2009) which is in line with the later
findings of Bruchas and colleagues (2011) as well as Russell and colleagues (2014).
Conclusion
Although there may be many neurochemical mechanisms that play a role in depression
and addiction, one crucial neurological process that affects both disorders is the release of
dynorphin and activation of kappa-opioid receptors (KORs) as a biological stress response
(Bruchas et al., 2011; Chartoff et al., 2012; Russell et al., 2014). Multiple studies have found that
the activation of KORs by dynorphin is responsible for depressive-like symptoms, particularly in
drug users (Chartoff et al., 2012; Russell et al., 2014), which provides one possible explanation
for why those with substance abuse disorders develop comorbid depression over time.
Furthermore, results of multiple studies indicated sex-dependent difference in KOR activation
where males appeared to be more sensitive to dynorphin and KOR agonists (Wang et al., 2011,
Russell et al., 2014) which may also explain findings that males were more likely to suffer from
the comorbid disorders (Brown et al., 2011; Chen et al., 2013). Additional evidence of the role of
dynorphin and KORs come from a study which concluded that p38 MAPK, a protein kinase
activated by the dynorphin/KOR system, played a significant role in increasing serotonin
reuptake (Bruchas et al., 2011) which would also cause depressive effects. The role of
dynorphin, KORs, and serotonin should be further studied for a better understanding of their role
in depression and addiction and for the ability to enhance treatments.
Chapter 5: Treatment
As previously discussed, there are many issues regarding diagnosis of COD including
healthcare practitioner misdiagnosis, inability of the patient to recognize existing COD, and
failure of the patient to report symptoms of COD. However, once the correct diagnosis is given,
Comorbidity of Depression and Substance Abuse Disorders 29
deciding which treatment options are best for the patient is the next step. Also, because there are
a variety of factors that affect comorbid depression and drug addiction, it is essential to not only
analyze which existing treatments for either disorder would be effective and/or appropriate, but it
is equally important to develop unique approaches to handling symptoms, all of which can be
combined into one effective treatment program.
Twelve-Step Facilitative Therapy and Cognitive Behavioral Therapy
Twelve-Step facilitative (TSF) therapy is a type of treatment that leads participants
through twelve guiding steps during the session (Wells et al., 2014). This method seeks to
encourage frequent attendance as well as outside practices such as journaling and forming a
relationship with a sponsor, someone who has gone through the program who can be of support (
Wells et al., 2014).
Cognitive Behavioral Therapy (CBT) is a popular type of psychosocial treatment that
encourages participants to consider social and/or environmental factors that could have
influenced them and contributed to their disorders as well as teaches users coping skills and
behaviors to help them manage their emotions, and in the case of substance abuse, urges to use
(Ling et al., 2013). CBT therapy can be done in individual or group sessions during which
trained counselors focus on identifying what triggers symptoms, episodes, or relapse of the
patients (Ling et al., 2013).
Integrated Cognitive Behavioral Therapy versus Twelve-Step Program
A study done by Lydecker and colleagues (2010) sought to determine whether integrated
cognitive behavioral therapy or a twelve-step program would be more effective in treating
veteran with comorbid SUD and MDD. Veterans that participated in the study were referred to
the 24-week program and diagnosed, using the DSM-IV, with comorbid depression and
Comorbidity of Depression and Substance Abuse Disorders 30
addiction (Lydecker et al., 2010). Researchers assessed substance use using the Time Line
Follow Back, depression symptoms using clinical The Hamilton Depression Rating Scale,
addiction severity using the Addiction Severity Index, clinical interviews, and the AA Affiliation
Scale to measure AA activity (Lydecker et al., 2010). They also assessed up to 12 months after
treatment (Lydecker et al., 2010). The researchers found that both treatments were successful yet
participants who underwent ICBT had more stable improvements at the six month checkup
however, they noted that they expected ICBT to have more significant improvements over the
TSF group but theorized that the less significant results could have been due to less ICBT
participants utilizing pharmacotherapy (Lydecker et al., 2010). These findings suggest that ICBT
may be more effective than TSF in treating the comorbid disorders and propose the possibility
that medication could play a significant role in patient outcome.
A study done by Worley and colleagues (2012) also compared treatments outcomes for
people with comorbid SUD and MDD who underwent either ICBT or TSF. They studied
participants with comorbid SUD and MDD, as diagnosed using DSM-IV, undergoing ICBT or
TSF with about 90% of participants on antidepressants in both conditions (Worley et al., 2012).
Group sessions for both conditions were held twice a week for 12 weeks and then once a week
for 12 weeks and researchers used latent growth curve models to analyze patient progress for up
to 12 months after treatment (Worley et al., 2012). They found that both groups had decreased
depressive symptoms and while there was a greater decline for the TSF group initially, there was
a greater decline for the ICBT group overall and a more significant improvement for substance
abuse (Worley et al., 2012). Those with improved depression showed improvements in substance
abuse and vice versa which researchers believe may be due to the relationship between the two
disorders (Worley et al., 2010; Worley et al., 2012), that is, relapses may trigger depressive
Comorbidity of Depression and Substance Abuse Disorders 31
symptoms and depressive symptoms may trigger relapse and the researchers note that
antidepressants may help with addiction for this reason (Worley et al., 2012). These findings
support the findings of Lydecker and colleagues (2010) and give more evidence of the
importance of ICBT as well as the significance of research into pharmacological interventions.
Medication
SSRI. As mentioned in the previous chapter, fluoxetine is a type of SSRI that has been
used for the treatment of depression (Chartoff et al., 2009; Cornelius et al., 2009; Cornelius et al.,
2011). Cornelius and colleagues have long studied the effects of fluoxetine and determined in
previous studies that adults with comorbid depression and alcohol abuse disorders were
randomly selected to receive fluoxetine or a placebo in a 12-week, double-blind trial where
weekly ratings of depression and alcohol consumption were measured (Cornelius et al., 1997).
Results showed that adults who were given fluoxetine showed improvement in depression and
alcohol use (Cornelius et al, 1997). Because researchers agreed with other studies such as the one
by Marmorstein (2010) that determined adolescents with depression could likely a predictor of
adults with comorbid depression and substance abuse, the group decided to investigate the
efficacy of fluoxetine in the treatment of adolescents (ages 15-20) with AUD and MDD as
diagnosed using DSM-IV (Cornelius et al., 2009). Along with either fluoxetine or a placebo,
participants received 9 sessions of group CBT and motivational enhancement therapy (MET)
during a twelve week period (Cornelius et al., 2009). Depressive symptoms were rated using the
Beck Depression Inventory. Results showed that fluoxetine did not appear to be effective in
treating symptoms for COD although both groups showed improvement overall, which
researchers reasoned may have been from CBT and/or MET (Cornelius et al., 2009). The
Comorbidity of Depression and Substance Abuse Disorders 32
researchers speculate that this may have been evident of a “placebo effect” among those who did
not receive the fluoxetine (Cornelius et al., 2009).
The researchers also discussed limitations such as small sample size which may have
contributed to skewed results (Cornelius et al., 2009) so they did an extension of this research in
a two-year follow-up evaluation to determine long-term efficacy of the treatment (Cornelius et
al., 2011). Researchers believed that at that time of the experiment, CBT was effective for CODs
and that MET was useful for increasing motivation and engagement in therapy and may have
contributed to helping with COD conditions overall (Cornelius et al., 2009; Cornelius et al.,
2011). Researchers also found that those who had CBT and MET treatment were more
successful after completing the two year follow-up (Cornelius et al., 2011). They did not notice a
significant difference in success of CBT and MET between those who received fluoxetine and
those who received a placebo however, they stated that the role of fluoxetine in the group’s
success was still unclear due to possible placebo effects (Cornelius et al., 2011). Results of the
study suggest that while fluoxetine may be helpful in decreasing symptoms for comorbid
depression and alcohol abuse disorders, as shown in the original study (Cornelius et al., 1997)
and may still be a useful treatment option, CBT and MET may be more effective.
Davis and colleagues (2010) also investigated SSRI medication efficacy for those with
major depressive disorders and substance use disorders. In this study, they sought to examine the
antidepressant medication citalopram used by those with MDD and SUD versus those with MDD
alone (Davis et al., 2010). They assessed participants using the 16-item Quick Inventory of
Depressive Symptomatology-Clinician-rated assessment and the Psychiatric Diagnostic
Screening Questionnaire (Davis et al., 2010). Participants included those with MDD only, with
MDD and alcohol use disorders, MDD and drug use disorder, and those with MDD, AUD, and
Comorbidity of Depression and Substance Abuse Disorders 33
drug use disorder (Davis et al., 2010). Improvements with citalopram were found for all groups
and there was no difference between the groups in terms of citalopram efficacy however those
with MDD and SUD were less successful at achieving remission and/or spent less time in
remission (Davis et al., 2010).
SSRI and Opioid Receptor Antagonist. Although Cornelius and colleagues were unsuccessful
in determining whether or not an SSRI would be as useful in adolescence as it was in adults
(Cornelius et al., 1997; Cornelius et al., 2011), the success of SSRIs in adults with depression is
well known has had prompted more research regarding whether or not it may be successful in
comorbid adults. Pettinati and colleagues (2010) sought to determine whether or not
antidepressants were effective in treating addition symptoms of those with comorbid addiction
and major depressive disorder (MDD) and conducted a double-blind, placebo-controlled
experiment consisting of participants with the co-occurring disorders who were given either
sertraline, a SSRI, naltrexone, an opioid receptor antagonist for alcohol dependence, both, or
placebos (Pettinati et al., 2010). Participants were diagnosed using DSM-IV and underwent
treatment for 14 weeks where they were assessed using self-report, HAM-D for depression and
the Addiction Severity Index (Pettinati et al., 2010). They found that patients with COD, a
combination of pharmacotherapies worked the most effectively, that is, a greater percentage of
patients using sertraline and naltrexone achieved abstinence and lower rates of depression
(Pettinati et al., 2010). Researchers found no significant advantages were found comparing the
two drugs separately (Pettinati et al., 2010), suggesting that medication as a form of treatment
can be highly successful for those with comorbid disorders as long as medications treat
symptoms of both disorders .
Combination Therapy
Comorbidity of Depression and Substance Abuse Disorders 34
Many researchers have come to the conclusion that for patients who suffer from
comorbid depression and substance abuse disorders, a combination of some the aforementioned
treatments would lead to the most successful in managing the disorders and their symptoms
(Hunter et al., 2012; Osilla, Hepner, Munoz, Woo, & Watkins, 2009; Watkins et al., 2011).
Hunter and colleagues (2012) sought to gain a better understanding of how to treat COD
patients by designing a randomized control trial where patients either received their typical
substance abuse treatment or their usual treatment with cognitive behavioral therapy. The
researchers found that those who received the combination therapy responded better to COD
symptoms than those who did not and that those who received combination therapy had more
positive attitudes regarding treatment and outcomes (Hunter et al., 2012).
Similarly, Watkins and colleagues (2011) designed a study to assess the efficacy of
cognitive behavioral treatments for those with comorbid depression and addiction by having
some participants receive substance abuse treatment only and others receive substance abuse
treatment with cognitive behavioral therapy; some of the patients in each group also received
medication. Results indicated that those who received drug treatment and cognitive behavioral
therapy in addition to their substance abuse treatment were significantly more successful in
handling their COD symptoms, reporting fewer relapses and decreased depressive symptoms
(Watkins et al., 2011).
Osilla, Hepner, Munoz, Woo, and Watkins (2009) designed a study similar to that of
Hunter and colleagues (2012) and Watkins and colleagues (2011), however, this group of
research focused not only on efficacy of combined treatment but feasibility as well. A substance
abuse treatment plan incorporating cognitive behavioral therapy was designed and counselors
who were to lead the sessions were given thorough training. When analyzing participant
Comorbidity of Depression and Substance Abuse Disorders 35
feedback, researchers found that overall, patients felt as though they were more informed about
their co-occurring disorders and better understood the comorbidity, believed the therapy could be
applied to their everyday lives, and felt that the integrated program was more useful than
substance abuse therapy alone (Osilla et al., 2009). Furthermore, staff at the treatment facilities
also felt positively about the efficacy of the combined treatment program however, there were
concerns from the staff regarding feasibility of providing this treatment long-term due to factors
such as cost of running the program and amount of training required of counselors (Osilla et al.,
2009).
Conclusion
In this chapter several types of treatment options for co-occurring depression and
substance abuse disorder were discussed. Multiple studies suggested compared integrated
cognitive behavioral therapy (ICBT), a psychosocial treatment that encourages participants to
consider factors that could contributed to their disorders as well as teaches users coping skills
(Ling et al., 2013), to twelve-step facilitation (TSF), a form of therapy where participants are
lead through twelve guiding steps (Wells et al., 2014). The researchers in the studies concluded
that ICBT may be more effective than TSF in treating the comorbid disorders and propose the
possibility that medication could play a significant role in patient outcome (Lydecker et al.,
2010; Worley et al., 2010; Worley et al., 2012). Researchers also investigated the role of
selective serotonin reuptake inhibitors, which are known to improve symptoms of depression, in
comorbid adults and adolescents however; they failed to determine a causal relationship between
the medication and symptom improvements (Davis et al., 2010; Cornelius et al., 2011). In one
study, participants were given a SSRI and an opioid receptor antagonist for alcohol dependence,
both, or placebos and it was determined that those who received both medications had the most
Comorbidity of Depression and Substance Abuse Disorders 36
significant symptom improvement, suggesting that a combination of medication works best for
the comorbid disorders (Pettinati et al., 2010). Studies that combined TSF, ICBT, and
antidepressant medications also had results indicating significant condition improvement (Osilla
et al., 2009; Watkins et al., 2011; Hunter et al., 2012)
Chapter 6: Research Proposal
Based on the studies previously discussed, it is evident that a combination of therapies
would be the most effective treatment for those with comorbid depression and substance
addiction. However, none of the aforementioned studies has combined TSF, ICBT, SSRI
medication and a medication that works as an opioid receptor antagonist. With that said, I will
conduct a study with combinations of all four types of therapies to determine which treatment
combination will be the most effect for those with comorbid depression and substance addiction.
I hypothesize that the group that undergoes TSF and ICBT with SSRI medication and an opioid
receptor antagonist will experience the most significant decrease in symptoms of the disorders.
Method
Participants
There will be a total of 220 participants in the study, all of whom must have been
diagnosed, following criteria and guidelines of the DMS-V, with comorbid depression and
alcohol abuse disorders. The participants will be referred to by a psychologist or psychiatrist and
will undergo mental health screenings before beginning treatment to confirm diagnosis.
Materials
Measures. The DSM-V criteria will be used to diagnose patients prior to the start of the
study. A survey on demographic information as well as family history of depression and/or
substance abuse disorders will be given to participants. To determine severity of substance abuse
Comorbidity of Depression and Substance Abuse Disorders 37
and depression, the Addiction Severity Index, a 45 minute structured interview, will be used as
outlined by Pettinati and colleagues (2010). The 24-item HAM-D will be used to measure
depression symptom severity (Pettinati et al., 2010).
Medication. The medication regimen will follow the design of Pettinati and colleagues
(2010) where participants who were randomly assigned to receive medication will take sertraline
(200mg/day) and naltrexone (100mg/day) for the duration of the experiment.
Procedure
There will be seven experimental groups: those on medication only, those who undergo
substance abuse treatment only in the form of TSF, CBT therapy only, medication and TSF,
medication and CBT, TSF and CBT, or those who undergo both types of therapy and have
medication. There will also be four control groups to account for possible placebo effects: those
with placebo only, placebo and TSF, placebo and CBT, and both therapies with placebo. This
will give a total of eleven groups and there will be a total of 20 participants randomly placed in
each group.
The experiment will follow a design similar to that of Osilla and colleagues (2009) where
participants who receive therapy will attend 18 sessions of group therapy. The group sessions
will be held once a week for a total of 18 weeks and each session will be one hour. Those who
only undergo ICBT or TSF will have 18 sessions of their respective therapies while the groups
that undergo both treatments will have nine sessions of each type of treatment. Each condition
will also be divided into two groups that attend sessions separately so that group sizes in therapy
sessions are 10 people to imitate the small group size in the Osilla experiment (Osilla et al.,
2009). Counselors will also undergo the same training as in the Osilla study (Osilla et al., 2009)
as will physicians to eliminate inconsistencies in diagnosis and treatment. Assessments will be
Comorbidity of Depression and Substance Abuse Disorders 38
taken prior to the start of the therapies, then weekly, and a 3-month and 6-month follow-up
assessment will also be done.
Expected Results
A MANOVA will be run to assess statistical outcomes. Participants’ improvements in
symptoms of depression and alcohol addiction will be tested. It is expected that the group that
undergoes TSF and ICBT with SSRI medication and an opioid receptor antagonist will
experience the most significant decrease in symptoms of the disorder when measured with the
Addiction Severity Index and HAM-D; all other groups with the exception of those who receive
placebo only will also experience symptom improvement and those who receive placebo only
will not experience changes in symptom severity (Osilla et al., 2009; Pettinati et al., 2010).
Discussion
Predictions
Based on previous findings involving combination therapy, it was hypothesized that the
group that undergoes TSF and ICBT with SSRI medication and an opioid receptor antagonist
will experience the most significant decrease in symptoms of the disorders when compared to all
other conditions. A large sample size was used as was a control group and random assignment.
This experiment design would help to show a cause and effect relationship between types of
therapies and severity of symptoms.
Limitations
Limitations of the study stem from the use of referrals and random assignment of
participants to groups. Because referrals from psychologists will be used to obtain participants, it
will not be possible to guarantee a representative population in the study which is significant due
to the gender, ethnic and socioeconomic status factors that affect the disorders. Also, because
Comorbidity of Depression and Substance Abuse Disorders 39
random assignment will be used, it will not be possible to guarantee that each group has the same
distribution of these factors or of severity.
Overall Conclusions
In conclusion, although there is still much research that needs to be done on the comorbid
relationship between addiction and depression, results have been found that appear to be
promising for improving the lives of those with the co-occurring disorders. Research examining
how the disorders may develop together including depression leading to self-medication through
substances, depression caused by substances used, or the disorders developing at the same time
(Worley et al., 2010; Suter et al., 2011; Marshall et al., 2012; Crum et al., 2013; Langas et al.,
2013). Errors in diagnosis which may be due to variation in patient assessment across
practitioners (Darghouth et al., 2012), attribution of patient symptoms to either depression or
substance addiction instead of recognizing that they suffer from both (Chan, Huang, Bradley, &
Unitzer, 2014; Mojtabai, Chen, Kaufmann, & Crum, 2014), and/or inaccurate self-reports by the
patient due to feelings of shame or fear (Mericle et al., 2012; Chen et al., 2013; Mojtabai et al.,
2014) have also been found.
Potential risk factors for developing comorbid depressive and substance abuse disorders
were examined. Genetic factors were found to play a large role in the development of the
disorders due to positive correlations of family history, gender, and developmental changes that
occur at early onset (i.e. adolescence), of either of the disorders (Lydecker et al., 2010;
Marmorstein, 2010; Marmorstein, et al., 2010; Brown et al., 2011; Chartoff et al., 2012; Chen et
al., 2013). Environmental factors were also established and it was shown that socioeconomic
status factors such as low income, low education, and unemployment are associated with the
development of depressive disorders and substance abuse as is prolonged stress and criminal
Comorbidity of Depression and Substance Abuse Disorders 40
history (Bruchas et al., 2011; Green et al., 2012; Jaffe et al., 2012l Chen et al., 2013;Langas et
al., 2013; Russell et al., 2014).
Studies found that the activation of KORs by dynorphin is responsible for depressive-like
symptoms and found sex differences in KOR activation (Wang et al., 2011; Chartoff et al., 2012;
Russell et al., 2014) which may explain findings that males were more likely to suffer from the
comorbid disorders (Brown et al., 2011; Chen et al., 2013).
Several types of treatment options for co-occurring depression and substance abuse
disorder have been researched including studies concluded that ICBT may be more effective than
TSF in treating the comorbid disorders (Lydecker et al., 2010; Worley et al., 2010; Worley et al.,
2012). Researchers also investigated the role of selective serotonin reuptake inhibitors yet results
were inconclusive (Davis et al., 2010; Cornelius et al., 2011). One study determined that those
who received multiple medications had the most significant symptom improvement, suggesting
that a combination of medication works best for the comorbid disorders (Pettinati et al., 2010).
Studies that combined TSF, ICBT, and antidepressant medications also had results indicating
significant condition improvement (Osilla et al., 2009; Watkins et al., 2011; Hunter et al., 2012)
Although these findings have made great differences in the understanding of the
relationship of comorbid depression and addiction, more work must be done in order to perfect
the diagnosis and treatment process. If results supported my hypothesis it would be influential in
the way practitioners choose to treat those with comorbid alcohol addiction and depression. My
proposed study should be extended to other abused substances, not just alcohol and other future
studies should examine the dynorphin and KOR system more closely as well as how the effect
serotonin. It is imperative to continue this research and conduct other future research because
Comorbidity of Depression and Substance Abuse Disorders 41
one will likely have to manage their symptoms for the rest of their lives, so finding the most
effective treatment to help overcome symptoms is crucial.
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