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

5.7 Major clinical issues with depression and benzodiazepine use

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• Sedative and depressive actions as well as long-term use of benzodiazepines exacerbate the negative symptoms of depression such as lack of energy, negative cognitions and anhedonia.
• Benzodiazepine use should be restricted to a few days with a long acting benzodiazepine.
• Psychological and behavioural treatment can be effective in treating insomnia.
• CBT for depression is more effective if there is minimal sedation and anxiolysis due to the benzodiazepine use.
• If long-term benzodiazepine use is being considered, then this should be administered under close supervision.

5.7.1 Effects of benzodiazepines on depression

• Benzodiazepines are often prescribed to relieve some of the symptoms of depression such as insomnia⁽¹⁸⁵⁾ and agitation during the acute treatment phase.
• However, benzodiazepines also cause disruptions to and reductions in Rapid Eye Movement (REM) sleep^{(186, 187)}.
• Sedative and depressive actions as well as long-term use of benzodiazepines exacerbate the negative symptoms of depression such as lack of energy, negative cognitions and anhedonia⁽⁵⁹⁾.

5.7.2 Interactions between benzodiazepines and therapeutic agents for depression

• There is an increased risk of sedation and overdose with the combination of benzodiazepines and sedative antidepressants such as tricyclics and mirtazepine^x.
• Benzodiazepines and antidepressants are both metabolised by CYP 450 enzymes which may result in the inhibition or induction of either drug group. Therefore, individuals should be monitored closely to ensure outcomes are appropriate^x.
• Fluvoxamine will inhibit the metabolism of alprazolam, midazolam, triazolam and diazepam causing increased sedation and potential toxicity^x.
• Citalopram and sertraline are the least likely SSRIs to have cytochrome-mediated drug interactions^x.

5.7.3 Management approaches to comorbid depression and benzodiazepines

• Benzodiazepine use should be discouraged and cessation should be a long-term goal.
• Antidepressant medication (SSRIs or other non-sedating antidepressants) can be commenced with the patient still taking benzodiazepines.
• Tolerance quickly develops to the effects of benzodiazepines used during the treatment of depression (acute agitation, anxiety, panic and insomnia)⁽¹⁸⁸⁾.
• Benzodiazepine use should be restricted to a few days with a long-acting benzodiazepine⁽¹⁸⁹⁾.
• Psychological and behavioural treatment can be effective in treating insomnia***^(190-192) associated with psychiatric disorders⁽¹⁹³⁾ and may reduce the need for benzodiazepine use during depression.
• CBT for depression will be more effective if there is minimal sedation and anxiolysis due to the benzodiazepine use.
• If large quantities of benzodiazepines (e.g. 40mg diazepam daily equivalent or more) are being consumed, then inpatient withdrawal to lower levels should be considered to avoid and manage seizure risk⁽¹⁹⁴⁾.
• If dependence has developed, then graduated withdrawal through slow reduction of dosage should be commenced****^(194-196), possibly after transferring the patient onto a long acting benzodiazepine.
• If long-term benzodiazepine use is indicated, then:
  • This should be subject to a contract with the patient.
  • Authorities should be advised, including registration with the relevant local government health authority.
  • The seeking of additional benzodiazepines from other prescribers should be monitored (e.g. using the Authority to release personal PBS claims information to a third party form)
  • Daily or weekly dispensing of benzodiazepines should be considered and may assist with controlling use.

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