Opioid use remits, depression remains

Case Forgetful and depressed
Mr. B, age 55, has been a patient at our clinic for 8 years, where he has been under our care for treatment-resistant depression and opi­oid addiction [read about earlier events in his case in “A life of drugs and ‘downtime’” Current Psychiatry, August 2007, p. 98-103].¹ He reports feeling intermittently depressed since his teens and has had 3 near-fatal suicide attempts.

Three years ago, Mr. B reported severe depressive symptoms and short-term memory loss, which undermined his job performance and contributed to interpersonal conflict with his wife. The episode has been continuously severe for 10 months. He was taking sertra­line, 150 mg/d, and duloxetine, 60 mg/d, for major depressive disorder (MDD) and sublin­gual buprenorphine/naloxone, 20 mg/d, for opioid dependence, which was in sustained full remission.² Mr. B scored 24/30 in the Mini- Mental State Examination, indicating mild cognitive deficit. Negative results of a com­plete routine laboratory workup rule out an organic cause for his deteriorating cognition.

How would you diagnose Mr. B’s condition at this point?
a) treatment-resistant MDD
b) cognitive disorder not otherwise specified
c) opioid use disorder
d) a and c

The authors' observations
Relapse is a core feature of substance use dis­orders (SUDs) that contributes significantly to the longstanding functional impairment in patients with a mood disorder. With the relapse rate following substance use treat­ment estimated at more than 60%,³ SUDs often are described as chronic relapsing conditions. In chronic stress, corticotropin-releasing factor (CRF) is over-sensitized; we believe that acute stress can cause an unhealthy response to an over-expressed CRF system.

To prevent relapse in patients with an over-expressed CRF system, it is crucial to manage stress. One treatment option to con­sider in preventing relapse is mindfulness-based interventions (MBI). Mindfulness has been described as “paying attention in a particular way: on purpose, in the present moment, and non-judgmentally.” In the event of a relapse, awareness and acceptance fostered by mindfulness may aid in recogniz­ing and minimizing unhealthy responses, such as negative thinking that can increase the risk of relapse.

History Remission, then relapse
Mr. B was admitted to inpatient psychiatric unit after a near-fatal suicide attempt 8 years ago and given a diagnosis of MDD recurrent, severe with­out psychotic features. Trials of sertraline, bupro­pion, trazodone, quetiapine, and aripiprazole were ineffective.

Before he presented to our clinic 8 years ago, Mr. B had been taking venlafaxine, 75 mg/d, and mirtazapine, 30 mg at bedtime. His previous outpatient psychiatrist added methylphenidate, 40 mg/d, to augment the antidepressants, but this did not alleviate Mr. B’s depression.

At age 40, he entered a methadone pro­gram, began working steadily, and got married. Five years later, he stopped methadone (it is unclear from the chart if his psychiatrist initiated this change). Mr. B’s depression persisted while using opioids and became worse after stopping methadone.

We considered electroconvulsive therapy (ECT) at the time, but switching the anti­depressant or starting ECT would address only the persistent depression; buprenor­phine/naloxone would target opioid crav­ing. We started a trial of buprenorphine/ naloxone, a partial μ opioid agonist and ĸ opioid antagonist; ĸ receptor antagonism serves as an antidepressant. He responded well to augmentation of his current regimen (mirtazapine, 30 mg at bedtime, and venlafax­ine, 225 mg/d) with buprenorphine/naloxone, 16 mg/d.^4,5 he reported no anergia and said he felt more motivated and productive.

Mr. B took buprenorphine/naloxone, 32 mg/d, for 4 years until, because of concern for daytime sedation, his outpatient psychia­trist reduced the dose to 20 mg/d. With the lower dosage of buprenorphine/naloxone ini­tiated 4 years ago, Mr. B reported irritability, anhedonia, insomnia, increased self-criticism, and decreased self-care.

How would you treat Mr. B’s depression at this point?
a) switch to a daytime antidepressant
b) adjust the dosage of buprenorphine/ naloxone
c) try ECT
d) try mindfulness-based cognitive therapy

The authors’ observations
Mindfulness meditation (MM) is a medi­tation practice that cultivates awareness. While learning MM, the practitioner inten­tionally focuses on awareness—a way of purposely paying attention to the present moment, non-judgmentally, to nurture calmness and self-acceptance. Being con­scious of what the practitioner is doing while he is doing it is the core of mindful­ness practice.⁶

Mindfulness-based interventions. We rec­ommended the following forms of MBI to treat Mr. B:
• Mindfulness-based cognitive therapy (MBCT). MBCT is designed to help people who suffer repeated bouts of depression and chronic unhappiness. It combines the ideas of cognitive-behavioral therapy (CBT) with MM practices and attitudes based on culti­vating mindfulness.⁷
• Mindfulness-based stress reduction (MBSR). MBSR brings together MM and physical/breathing exercises to relax body and mind.⁶

Chronic stress and drug addiction
The literature demonstrates a significant association between acute and chronic stress and motivation to abuse substances. Stress mobilizes the CRF system to stimulate the hypothalamic-pituitary-adrenal (HPA) axis, and extra-hypothalamic actions of CRF can kindle the neuronal circuits responsible for stress-induced anxiety, dysphoria, and drug abuse behaviors.⁸

A study to evaluate effects of mindful­ness on young adult romantic partners’ HPA responses to conflict stress showed that MM has sex-specific effects on neu­roendocrine response to interpersonal stress.⁹ Research has shown that MM practice can decrease stress, increase well-being, and affect brain structure and func­tion.¹⁰ Meta-analysis of studies of animal models and humans described how spe­cific interventions intended to encourage pro-social behavior and well-being might produce plasticity-related changes in the brain.¹¹ This work concluded that, by tak­ing responsibility for the mind and the brain by participating in regular mental exercise, plastic changes in the brain pro­moted could produce lasting beneficial consequences for social and emotional behavior.¹¹