Clinicians require a good understanding of the role of psycho-active medications in the treatment of mental illness and also the high risk of potential drug-drug interactions and side effects in the population with HIV infection. Certain antiretroviral drugs, in particular protease inhibitors and NNRTIs, are metabolised primarily by the cytochrome P450 3A4 and 2D6 hepatic microsomal isoenzymes, which can in turn inhibit or enhance their activity. Most psychotropic medications are also metabolised by, and can affect the activity of, these isoenzymes. Patients may also have serum protein anomalies resulting in an altered free fraction of protein-bound drugs. There is, therefore, a high potential for drug interactions when psychotropic agents are used in the setting of ART, making it important to use care and consult up-to-date drug information or an informed pharmacist before prescribing.
Commonly used agents in this population include antidepressant medications such as SSRIs to treat depression and anxiety disorders. SSRI medications that have less interaction with these enzymes (e.g. citalopram, escitalopram and sertraline) are preferred for use. Benzodiazepines are commonly prescribed for short-term use in anxiety disorders. However their half-lives can be signiﬁcantly prolonged by treatments and thus agents with shorter half-lives (e.g. oxazepam, temazepam and lorazepam) are preferred. Similarly mood stabilisers, such as sodium valproate and carbamazepine, and antipsychotics can interact with certain antiretroviral drugs and care is required when prescribing.. Lithium is also used as a mood stabilising agent and although its metabolism is not impacted on by hepatic enzymes, its use warrants careful monitoring in the medically unwell due to its narrow therapeutic window.
In considering the impact of antiviral medications on psychological health it is important to be aware that, although antiviral medications can be targeted towards improvement in CNS symptoms, there are specific adverse effects on mood and sleep cycles of some of these medications. A review of the AIDS Clinical Trials Group antiviral naive studies looked at the association between efavirenz and suicidal thinking and behaviour. This analysis indicated a two fold increase in the hazard of suicidality compared to non-efavirenz antiviral regimens.  When constructing an effective antiretroviral medication regimen that includes efavirenz as a component, consideration should be given to a history of mental illness and suicidal or self-harm behaviours and appropriate mental health supports be included in the treatment plan.