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

[email protected]


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.


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


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


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


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


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.


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”).


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


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.


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


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.


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


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


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


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


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.


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


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).


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


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


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).


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


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


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


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


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


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,


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


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


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


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


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


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


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


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


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


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


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


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


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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Comorbidity of Depression and Substance Abuse Disorders- Risk Factors, Effects, and Treatment

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