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Comorbidity of mental disorders and substance use: a brief guide for the primary care clinician

5.5 Major clinical issues with depression and opioid use

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Rates of depression decrease once people enter treatment for opioid dependence, in particular, maintenance pharmacotherapies.
Fluvoxamine^xxx, fluoxetine^xx, norfluoxetine^xx and paroxetine^x can inhibit buprenorphine and methadone metabolism through inhibition of the CYPs involved in their metabolism.
Carbamazepine is a potent CYP inducer and will induce the metabolism of methadone and buprenorphine as well as reduce plasma concentrations.
If antidepressant medications are to be used, then non-sedating antidepressants (such as SSRIs) are preferable due to the risk of overdose mentioned above with tricyclic antidepressants.
CBT provides additional benefit in combination with a maintenance therapy program in the treatment of depression in opioid users.

5.5.1 Effects of opioids on depression

Depression is common among illicit opioid users^(24-27). Heavier illicit opioid use is associated with more severe depression⁽²⁶⁾.
Rates of depression decrease once people enter treatment for opioid dependence, in particular maintenance pharmacotherapies^{(26, 146)}.
Conversely, continued illicit opioid use affects adherence to treatment for depression in opioid dependent people⁽¹⁴⁷⁾.

Fluvoxamine^xxx, fluoxetine^xx, norfluoxetine^xx and paroxetine^x can inhibit buprenorphine and methadone metabolism through inhibition of the CYPs involved in their metabolism^(148-150). This can result in an increase in plasma opioid pharmacotherapy concentrations and potential overdose. This can be a particular issue during induction onto methadone; however, the risk may persist even after stabilisation has occurred^xxx(151-155).
Fluvoxamine is the most potent inhibitor of methadone and buprenorphine metabolism and is the most clinically relevant. Therefore, it should be avoided^xxx(150).
Fluoxetine and paroxetine should also be avoided^xx.
Citalopram and sertraline are the least likely SSRIs to have cytochrome-mediated drug interactions; however, due to the theoretical potential for an interaction, caution should still be used and individuals monitored closely^x(156).
Carbamazepine is a potent CYP inducer and will induce the metabolism of methadone and buprenorphine as well as reduce plasma concentrations^{xx(149, 157)}. This has the potential to result in withdrawal and failure of retention in treatment****^(158-160).
There is an increase in sedation as well as risk of fatal overdose with opioid use and tricyclic antidepressants^xx(161).

It is important to consider the variety of factors that may be contributing to depressed mood in this group of people, e.g. chronic psychosocial stressors, the effects of substance dependence, and longstanding personality-related mood disturbances.
Entry into a maintenance pharmacotherapy (buprenorphine or methadone) is associated with improvement in depression***⁽¹⁴⁶⁾.
There is conflicting evidence on the efficacy of antidepressant medication amongst maintenance therapy populations****^(162-165).
If antidepressant medications are to be used, then non-sedating antidepressants (such as SSRIs) are preferable due to the risk of overdose mentioned above with tricyclic antidepressants.
CBT provides additional benefit in combination with a maintenance therapy program in the treatment of depression in opioid users.
In individuals who adhere to medication plans, naltrexone in combination with antidepressants is effective in improving depression and reducing illicit opioid intake***^{(142, 164, 166)}.
In individuals who adhere to medication plans, naltrexone treatment is associated with reduced depression compared with methadone maintenance treatment***^{164, 166)}.