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

10.7 Major clinical issues with somatoform disorders and benzodiazepine use

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• People with somatoform disorders often use benzodiazepines to alleviate anxiety symptoms or to moderate pain, frequently resulting in benzodiazepine dependence.
• Emphasis should always be placed on non-medication management of the somatoform disorder as a first line of treatment.
• CBT has shown reductions in somatic symptoms and improved functioning in people with somatoform disorders.
• In general, use of benzodiazepines should be discouraged due to its dependence potential and psychomotor effects.

10.7.1 Effects of benzodiazepines on somatoform disorders

• People with somatoform disorders often use benzodiazepines to alleviate anxiety symptoms or to moderate pain, frequently resulting in benzodiazepine dependence^{(377, 404)}.
• Short-acting benzodiazepines, in particular, may result in fluctuating plasma concentrations. These may result in exacerbation of anxiety symptoms when levels are low resulting in frequent attendances at health services.

10.7.2 Interactions between benzodiazepines and therapeutic agents for somatoform disorders

• Benzodiazepines, opioids and antidepressants are metabolised by CYP 450 enzymes which may result in the inhibition or induction of each drug group. Therefore, individuals should be monitored closely to ensure they are receiving the appropriate therapeutic effect and not experiencing increased sedation which may result in impaired driving, injury and, in extreme cases, overdose^x.
• Methadone itself has been shown to inhibit CYP3A4^{xx(240, 241)} which also metabolises many benzodiazepines. This has the potential to increase plasma concentrations of benzodiazepines and increase their sedative effects^{x(242, 243)}.
• Several deaths have been reported due to benzodiazepine use in conjunction with high dose buprenorphine and may be a result of similar metabolic interactions^xxx(244-246).
• 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).

10.7.3 Management approaches to comorbid somatoform disorders and benzodiazepine use

• Emphasis should always be placed on non-medication management of the somatoform disorder as a first line of treatment when the resources are available and the client is willing to engage.
• CBT has shown reductions in somatic symptoms and improved functioning in people with somatoform disorders****^(380-386).
• In general, use of benzodiazepines should be discouraged due to its dependence potential and psychomotor effects.
• If large quantities of benzodiazepines (e.g. 40mg diazepam daily equivalent) 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.
• If the person is ready for change and willing to engage in CBT specifically for their somatoform disorder, then minimisation of benzodiazepine dosage is required so that the CBT can have greater effectiveness.
• Benzodiazepines are frequently prescribed to induce 'muscle relaxation'. However, large doses are often required (up to 40mg diazepam equivalents per day) which will not be conducive to rehabilitation.
• Use of antidepressants may be required for comorbid depression and anxiety***^{(406, 407)}, with tricyclics being useful⁽³⁷⁷⁾ for aiding chronic tension headaches and fibromyalgia.

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