A randomised, controlled trial of fluoxetine in methadone maintenance patients with depressive symptoms

doi:10.1016/S0165-0327(01)00419-0

Journal of Affective Disorders

Volume 72, Issue 1, October 2002, Pages 85-90

https://doi.org/10.1016/S0165-0327(01)00419-0 Get rights and content

Abstract

Background: Depression and antidepressant use are prevalent in methadone maintenance patients (MMPs). However, antidepressant efficacy is not well established in this population. This study examined the efficacy of fluoxetine in improving depressive symptoms and reducing substance use in MMPs. Methods: Stabilised MMPs scoring over 21 on the Beck Depression Inventory were randomised to receive fluoxetine or placebo over 12 weeks. Results: Forty-nine subjects were randomised. In both groups, significant improvements were observed in depression, life functioning, and social impairment over 12 weeks. Poly-drug use improved in completers only. No fluoxetine effects were observed. Conclusions: Little evidence supports use of fluoxetine as a treatment for depressive symptoms in MMPs.

Introduction

Comorbid depression is prevalent in methadone maintenance patients (MMPs) (Brooner et al., 1997) and is related to poor psychosocial outcomes, needle sharing and relapse (Rounsaville et al., 1982, Rounsaville et al., 1986, Crawford, 1996).

Antidepressant trials in MMPs have had mixed results. Some studies (e.g. Nunes et al., 1998) found an antidepressant to be superior to placebo, whilst others (Kleber et al., 1983, Petrakis et al., 1998) reported no differences between antidepressant and placebo.

The effects of antidepressants on substance use are also unclear, especially benzodiazepine use, which is common in Australian MMPs (Darke et al., 1993). This study examined the efficacy of fluoxetine in reducing depression and substance use in MMPs, and whether improved mood assisted in reducing substance use.

Section snippets

Subjects

Self-referred subjects were screened using the Beck Depression Inventory (BDI) (Beck et al., 1961); those scoring above 21 were eligible to participate. Given the difficulty diagnosing depression in substance users (Kranzler et al., 1995), the tendency for antidepressants to be prescribed for substance use (Olfson et al., 1998), and high rates of antidepressant use in this population (Roszell and Calsyn, 1986, Darke and Ross, 2000), the sample was intended to represent MMPs for whom

Results

Forty-nine subjects (33 men) were randomised (age range 23–49 years). Subject characteristics are detailed in Table 1. There were no differences between subjects receiving fluoxetine and placebo.

Fifteen subjects did not complete the study (10 on fluoxetine). Non-completers were more likely to have used antidepressants before (P<0.05) and tended to have higher initial BDI scores (P=0.059) than completers. No other differences were observed.

Using ITT analysis, depressive symptoms and functioning

Discussion

Fluoxetine had no differential effect on depressive symptoms. Both placebo and fluoxetine groups displayed improvement in depressive symptoms over time, suggesting that first-line use of fluoxetine in MMPs with depressive symptoms may not be appropriate. Some relationships were observed between mood and drug use, but these remain inconclusive. The relationship between depression, substance use and antidepressant use remains to be clarified.

Our findings, similar to those of Petrakis et al. (1998)

Acknowledgements

Eli Lilly Ltd. provided financial support. We thank Bayside Clinic, Clinic 36, Rankin Court, The Langton Centre; and John Saunders for his helpful criticism. The late David Mascord will be remembered and appreciated for his friendship and support.

References (33)

S. Darke et al.
Drug use, HIV risk-taking behaviour and psychosocial correlates of benzodiazepine use among methadone maintenance clients
Drug Alcohol Depend.
(1993)
H.R. Kranzler et al.
Validity of psychiatric diagnoses in patients with substance use disorders: is the interview more important than the interviewer?
Comp. Psychiatry
(1995)
M. Lader
Anxiety or depression during withdrawal of hypnotic treatments
J. Psychosom. Res.
(1994)
K.M. Mattocks et al.
Placebos, active control groups, and the unpredictability paradox
Biol. Psychiatry
(2000)
G. Parker et al.
A brief self report depression measure assessing mood state and social impairment
J. Affect. Disord.
(1994)
I. Petrakis et al.
Fluoxetine treatment of depressive disorders in methadone maintained opioid addicts
Drug Alcohol Depend.
(1998)
J.G. Rabkin et al.
Baseline characteristics of 10-day placebo washout responders in antidepressant trials
Psychiatr. Res.
(1987)
H. Ashton
Benzodiazepine withdrawal: outcome in 50 patients
Br. J. Addict.
(1987)
A.T. Beck et al.
An inventory for measuring depression
Arch. Gen. Psychiatry
(1961)
G. Bertschy et al.
Fluoxetine addition to methadone in addicts: pharmacokinetic aspects
Ther. Drug Monit.
(1996)

R.K. Brooner et al.

Psychiatric and substance use comorbidity among treatment-seeking opioid abusers

Arch. Gen. Psychiatry

(1997)

W.A. Brown

The placebo effect

Sci. Am.

(1998)

J.R.M. Caplehorn et al.

Methadone dosage and retention of patients in maintenance treatment

Med. J. Aust.

(1991)

V. Crawford

Comorbidity of substance misuse and psychiatric disorders

Curr. Opin. Psychiatry

(1996)

S. Darke et al.

Development and validation of a multi-dimensional instrument for assessing outcome of treatment among opiate users: the opiate treatment index

Br. J. Addict.

(1992)

S. Darke et al.

The use of antidepressants among injecting drug users in Sydney, Australia

Addiction

(2000)

Cited by (28)

Opioid agents for treatment-resistant depression
2022, Managing Treatment-Resistant Depression: Road to Novel Therapeutics
Treatment-resistant depression (TRD) is a major public health problem in terms of prevalence, individual suffering, and cost for society, and it is commonly associated with significant disability and psychosocial impairment worldwide. Despite recent advances in the effort to identify the neurobiological correlates of TRD, the pathophysiology of this condition still remains unclear. The opioid system is known to be involved in stress responses, mood, reward, and hedonic responses. Relevantly, this system is important for modulating dopaminergic (DA), serotonergic (5-HT) and noradrenergic (NA) systems, synaptic plasticity, neurogenesis in the hippocampus, hypothalamic-pituitary-adrenal gland (HPA) axis functioning, and brain-derived neurotrophic factor (BDNF) activity; and it is dysregulated in depressive disorders, as well.
Emerging approaches to address endogenous opioid dysregulation in MDD may yield novel therapeutics associated with reduced or absent risk of abuse or addiction. The present chapter illustrates the psychoactive medications related to the opioid system which may be considered in treating TRD, their mechanisms of action, pharmacokinetics, efficacy, and adverse effects. The most relevant clinical studies of all these drugs have been here summarized with a particular focus on efficacy and safety of these drugs.
Frontal cortex dysfunction as a target for remediation in opiate use disorder: Role in cognitive dysfunction and disordered reward systems
2018, Progress in Brain Research
Citation Excerpt :
For example, Petrakis et al. (1998) reported that a 12-week course of fluoxetine failed to produce improvements in MDD symptoms above placebo. This finding has been replicated in other studies using fluoxetine (Dean et al., 2002) and sertraline (Carpenter et al., 2004). Thus, although more study is required to make a definitive claim on the effectiveness of SSRIs in OUD-associated mood dysfunction, the available evidence suggests that SSRI antidepressants are ineffective.
In this chapter, we develop a model of μ- and δ-opioid receptor (OR) effects on cellular activity in the corticostriatal circuit after reviewing clinical data on cognitive and mood impairments in opioid substance use disorder (OUD), we use this model to derive information on the relevance of opioid actions in this circuit for cognition and reward. We find that the cognitive impairments and rewarding properties of acute μ-OR activation can reasonably explained by pharmacological actions in the corticostriatal circuit. However, long-term cognitive impairments and mood dysfunction observed in OUD are probably induced by opiate abuse-related degenerative mechanisms.
Comorbidity – Depression
2010, Encyclopedia of Behavioral Neuroscience, Three-Volume Set, 1-3
Comorbidity - Depression
2010, Encyclopedia of Behavioral Neuroscience
Agency and dependency within treatment: Drug treatment clients negotiating methadone and antidepressants
2007, Social Science and Medicine
This paper explores how drug treatment clients exercise agency while finding their ability to act curtailed by the strictures of treatment itself. Drawing on qualitative interviews with 77 male and female drug treatment clients collected in an Australian study of drug treatment and mental health, the experience of methadone maintenance treatment (MMT) and that of commonly prescribed medications for depression (antidepressants) are examined. The ways that clients engage with MMT and antidepressants are detailed, illustrating how both types of treatment can make clients feel dependent, but can also motivate clients to modify their treatment regimens. These modifications are “tactical” responses generated within the constraints of treatment regulations and can also be against clinical recommendations e.g. stopping treatment. Rather than seeing this as “non-compliance”, it is suggested that the negotiation of treatment is an inevitable response of clients trying to adapt to imperfect treatment conditions, who may have understandable anxieties about taking medication. The ways in which treatment providers might better acknowledge the capacities of MMT clients to engage with or modify treatment are discussed, as is the need to acknowledge drug treatment clients’ anxieties about dependency and pharmaceutical drugs.
Efficacy of antidepressants in substance use disorders with and without comorbid depression: A systematic review and meta-analysis
2005, Drug and Alcohol Dependence
Antidepressants are commonly used in substance abusers due to the potential effect on some underlying mechanisms involved in drug use disorders and to treat comorbid depression. A systematic review of the literature of the efficacy of antidepressant drugs in subjects with drug abuse disorders, including alcohol, cocaine, nicotine and opioid, with and without comorbid depression was performed. Only randomised, double-blind, controlled trials have been evaluated. A meta-analysis was done with the included studies that used common evaluation procedures in alcohol, cocaine and opioid dependence. Based on the present review some recommendations may be proposed.
The prescription of antidepressants for drug abuse seems only clear for nicotine dependence with or without previous comorbid depression (bupropion and nortryptiline). In alcohol dependence without comorbid depression, the use of any antidepressant seems not justified, while in cocaine dependence has to be clarified. The use of antidepressants in alcohol, cocaine or opioid dependence with comorbid depression needs more studies in well-defined samples, adequate doses and duration of treatment to be really conclusive. Interestingly, SSRIs do not seem to offer significant advantages compared with tricyclic drugs in substance abuse disorders. Differences both related to individual characteristics and specific antidepressant drugs need to be clarified in future studies.

View all citing articles on Scopus

View full text

Brief reportA randomised, controlled trial of fluoxetine in methadone maintenance patients with depressive symptoms

Abstract

Introduction

Section snippets

Subjects

Results

Discussion

Acknowledgements

Drug Alcohol Depend.

Comp. Psychiatry

J. Psychosom. Res.

Biol. Psychiatry

J. Affect. Disord.

Drug Alcohol Depend.

Psychiatr. Res.

Benzodiazepine withdrawal: outcome in 50 patients

Br. J. Addict.

An inventory for measuring depression

Arch. Gen. Psychiatry

Fluoxetine addition to methadone in addicts: pharmacokinetic aspects

Ther. Drug Monit.

Psychiatric and substance use comorbidity among treatment-seeking opioid abusers

Arch. Gen. Psychiatry

The placebo effect

Sci. Am.

Methadone dosage and retention of patients in maintenance treatment

Med. J. Aust.

Comorbidity of substance misuse and psychiatric disorders

Curr. Opin. Psychiatry

Development and validation of a multi-dimensional instrument for assessing outcome of treatment among opiate users: the opiate treatment index

Br. J. Addict.

The use of antidepressants among injecting drug users in Sydney, Australia

Addiction

Brief report
A randomised, controlled trial of fluoxetine in methadone maintenance patients with depressive symptoms