Treatment Issues In DrugDependent Women With Comorbid Depression

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Treatment Issues In Drug-Dependent Women With
Comorbid Depression

• Rajita Sinha, Ph.D.
• Department Of Psychiatry
• Yale University School Of Medicine

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Disclosure Statement

• I have no significant or other relationship with
  the manufacturer of any product.

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Prevalence of Co-occurring Depression and Drug
Use Disorders
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Depression and Drug Dependence - Sex Differences

• Rates of drug dependence are 21 for men vs
  women.
• On the other hand, women have higher rates of
  major depression than men.
• Women with depression and anxiety disorders are
  at a higher risk of developing drug dependence
  than women without these psychiatric disorders.

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Self-Medication HypothesisDrug Use to Cope with
Emotional Distress
Emotional Distress as a Trigger (more common in
women)
THE CYCLE OF DRUG ABUSE
Drug Use Tolerance to drug
Chasing the High Avoid Negative Mood Craving
Self-medication High/ Stimulating Effect
Coming Down (Crash)/sedative Depressant
Effects Withdrawal-Related Distress
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Depression Alters Rewarding Effects of
Dextroamphetamine
Source Tremblay, BSc, Naranjo, C.A., Cardenas,
L., Herrmann, N. and Busto, U.E. (2002). Probing
Brain Reward System Function in Major Depressive
Disorder. Archives of General Psychiatry, 59
p.412
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Sex Differences in Effects of Trauma Exposure

• Early life stress, particularly childhood sexual
  abuse, is more common in women than men.
• Childhood abuse increases risk of psychiatric
  illness in women, more so than men.
• While rates of trauma are similar for men and
  women, women are 2-3 times more likely to develop
  PTSD as compared to men.
• Higher rates of anxiety disorders in women may
  also play a role in their higher risk of
  depression.

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Clinical Symptoms of Depression

• MDD Symptoms
• Sad/depressed mood for a 2-week period
• Loss of interest in natural rewards
• Sleep/eating problems
• Attention/concentration problems
• Irritability/restlessness
• Loss of energy
• Worthlessness feelings

• Drug Related Mood Symptoms
• Irritability/restlessness
• Depressed mood
• Eating/Sleep difficulties
• High drug craving
• Loss of interest in natural rewards
• Attention/concentration problems

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Altered Neurobiology in Depression and During
Drug Withdrawal
or
Adapted from Markou, A., Kosten, T., Koob, G.
(1998). Neuropsychopharmacology 18(3), p.141.
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Depression Drug Dependence Link in Women

• We have hypothesized that in women, presence of
  psychiatric disorders and the motivation to cope
  with distress through drugs increases the risk of
  developing drug addiction.
• This increased risk may be associated with
  changes in stress circuits possibly linked to
  pre-existing psychopathology that results in an
  altered subjective response to drugs of abuse.
• These changes in brain stress circuits continue
  to play a role in mediating the association
  between emotional distress and drug relapse in
  women.

Source Sinha R, Rounsaville BJ (2002). J of
Clinical Psychiatry, 63, 616-627
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Depression Scores Predicts of Drug Abstinence
Status (N827)

• Controlling for other variables that
  significantly predict abstinence
• Length of Stay
• Age
• Race
• Insurance Status
• Frequency of Drug Use at Admission
• Alcohol use

SOURCE Sinha, R., Dodge R (under review).
Depression Symptoms Predicts Drug Abstinence
Outcome. Psychiatric Services
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Social Burden/Support Factors Affecting Drug
Abusing Women

• Substance abusing women as compared to substance
  abusing men are
• More likely to live with a drug abusing conjugal
  partner.
• More likely to be introduced to drugs by a male
  partner.
• More likely to have the sole responsibility of
  children/minors.
• More likely to face the negative effects of the
  social stigma attached to substance abuse.

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Sex Differences in Stress Responses

• Sex differences in the HPA response to stress has
  been noted in numerous animal studies.
• In humans, women show a greater subjective
  response to stress but lower physiological and
  HPA response as compared to men.
• These responses vary by phase of the menstrual
  cycle and a greater stress response in the luteal
  phase of the cycle has been reported.
• Abnormalities in the stress response have been
  associated with PTSD, depression and early
  trauma, illnesses that are more common in women.

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Laboratory Model of Stress and Stress-Induced
Drug Craving

• Using a guided imagery based method of stress
  induction, weve found that brief exposure to
  personal stress and to drug cues when compared to
  neutral relaxing imagery in drug dependent
  individuals resulted in
• Increases in cocaine craving and anxiety,
• Increases in heart rate and blood pressure,
• Increases in hypothalamic pituitary adrenal axis
  measures such as cortisol, ACTH and prolactin
  levels.
• Increases peripheral catecholamine responses.

Published previously Sinha et al.,
Psychopharmacology, 1999 2000 2003.
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Main Effect Condition F(2, 901) 82.3, Adj.
p lt 0.0001 DC gt S gt N
Time point F(5, 901) 29.7, Adj. p lt 0.0001
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Main Effect Condition F(2, 901) 48.5, Adj.
p lt 0.0001 S gt DC gt N
Time point F(5, 901) 20.2, Adj. p lt 0.0001
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Main Effects Condition F(2, 828) 20.4,
Adj. p lt 0.0001 S gt DC gt N Time
Point F(5, 828) 7.9, Adj. p lt 0.0001
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Main Effect of Condition F(2, 663) 4.9, p lt
0.01 S gt N DC gt N
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Relapse Rates after Inpatient Treatment

• Follow-up rates were 92, i.e. 49 of 54 subjects
  successfully completed the 90-day follow-up
  interview.
• 34 or 65 of subjects had relapsed to cocaine use
  after inpatient cocaine treatment.
• No sex differences in rates of relapse were
  observed.

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Stress Drug Cues Neutral
No Relapse D gt S (plt.05) D gt N (plt.001)
Relapse S gt D (plt.0001) S gt N (plt.0001)
Relapse Group X Condition F2,726 7.5, plt.0006
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Stress Drug Cues Neutral
No Relapse D gt S (plt.02), DgtN (plt.06)
Relapse S gt D (plt.02) S gt N (plt.002)
Relapse Group X Imagery Condition F 2,5955.6,
plt.004
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Stress Drug Cues Neutral
No Relapse No Differences between conditions
Relapse S gt N (plt.001 S gt D (plt.0001)
Relapse Group X Condition F2,55110.4, plt.0001
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Sex Differences in Association Between Stress
Response and Cocaine Relapse

• In contrast to men, women showed a significant
  positive association between stress response, as
  measured by cortisol and NE and time to cocaine
  relapse.
• Furthermore, women who relapsed had greater
  cortisol and NE reactivity as compared to women
  who did not relapse and to men.

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Sex Differences in Association Between Stress and
Drug Cue Responses and Time to Cocaine Relapse
plt0.05
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Pharmacological Treatment Issues

• Evidence suggests that SSRIs and TCAs are of
  benefit in improving mood symptoms in drug
  dependent individuals with primary depression
  (data from cocaine, opiate, and alcohol dependent
  samples).
• Women are significantly underrepresented in these
  studies, so gender-specific efficacy has been
  difficult to obtain.
• It would be important to directly assess whether
  depressive symptoms and stress-associated
  responses are altered/normalized with SSRIs or
  TCAs in drug dependent women.

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Psychosocial Treatment Issues

• Cognitive Behavioral Approaches have shown
  efficacy in addressing mood related symptoms in
  drug dependent individuals
• Mood Management Training Includes specific
  sessions to address dysphoric mood and negative
  affect.
• Seeking Safety A new cognitive behavioral
  treatment for women with PTSD. It may be
  particularly useful for women with comorbid
  depression and PTSD/anxiety symptoms.
• Dialectical behavior Therapy (DBT) for Substance
  Abuse Shown to be effective for substance
  abusing women with borderline personality
  disorder, majority of who have MDD.

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Mood Management Modules

• Cognitive Behavioral sessions that target mood
  and negative affect and their influence on drug
  use behaviors (Hall et al., 1994). It includes
  the following interventions
• Daily monitoring of mood, negative thoughts, and
  drug use behaviors.
• Relationship between mood, negative thoughts, and
  drug use behaviors are discussed (functional
  chain analysis).
• Develop ways to increase pleasant non-drug
  related activities.
• Relaxation training, communication, and
  assertiveness training.
• Coaching on applying skills to high-risk
  situations.

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Seeking Safety (Najavits et al. 1998)

• Cognitive behavioral group psychotherapy for 24
  sessions. Safety is the highest priority. In
  addition coping skills to address the following
  themes are taught
• Asking for help
• Setting boundaries
• Self - nurturing skills
• Fighting triggers
• HIV risk

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DBT for Substance Abuse (Linehan et al. 1998)

• Cognitive behavioral approach that focuses on
  emotion dysregulation as a construct that
  influences drug use behaviors (Linehan et al.,
  1998). Interventions include
• Daily monitoring of emotions, other triggers,
  craving, and drug use behaviors.
• Behavior analysis of feelings, thoughts, urges,
  and actions.
• Focus on acceptance and change related skills.
• Specific skills training on mindfulness, distress
  tolerance, interpersonal effectiveness, and
  emotion regulation.
• Specific emphasis on skills coaching for skills
  generalizability to day-to-day life situations.

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Future Directions

• Pharmacological treatment studies addressing
  co-morbid disorders in drug dependence need to
  recruit adequate numbers of women to address
  gender-based hypotheses.
• Clinical research on mechanisms underlying
  specific addiction treatments should address
  gender factors linking depression and drug abuse.
• Gender related treatment differences in addiction
  have been found but we do not understand the
  underlying mechanisms for these differences.

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Acknowledgements

• Paul Maciejewski, Ph.D.
• Carolyn Mazure, Ph.D.
• Bruce Rounsaville, M.D.
• Thomas Kosten, M.D.

• Collaborators
• Robert Malison, MD
• Ned Cooney, PhD
• George Anderson, PhD
• Mary Jeanne Kreek, MD (Rockefeller University)

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Acknowledgements

• This research was supported by the NIH Office of
  Research on Women's Health and the National
  Institute on Drug Abuse.
• Support was also provided by the following NIH
  grants R01-DA11077, P50-DA16556 and M01-RR00125
  to Yale, and P60-DA05130 to the Laboratory on the
  Biology of Addictive Diseases at Rockefeller
  University.