Comparative effectiveness of dual-action versus single-action antidepressants for the treatment of depression in people living with HIV/AIDS

Highlights

• Dual-action and single-action antidepressants were compared in people with HIV.

• Both types of antidepressants are effective for depression in people with HIV.

• Both types of antidepressants are suitable 1st line treatments for people with HIV.

• Depression remission rates were lower than results observed in controlled trials.

• Comparisons of other health services for depression are needed in people with HIV.

Abstract

Background

Depression is the most common psychiatric comorbidity among people living with HIV/AIDS (PLWHA). Little is known about the comparative effectiveness between different types of antidepressants used to treat depression in this population. We compared the effectiveness of dual-action and single-action antidepressants in PLWHA for achieving remission from depression.

Methods

We used data from the Centers for AIDS Research Network of Integrated Clinic Systems to identify 1175 new user dual-action or single-action antidepressant treatment episodes occurring from 2005 to 2014 for PLWHA diagnosed with depression. The primary outcome was remission from depression defined as a Patient Health Questionnaire-9 (PHQ-9) score <5. Mean difference in PHQ-9 depressive symptom severity was a secondary outcome. The main approach was an intent-to-treat (ITT) evaluation complemented with a per protocol (PP) sensitivity analysis. Generalized linear models were fitted to estimate treatment effects.

Results

In ITT analysis, 32% of the episodes ended in remission for both dual-action and single-action antidepressants. The odds ratio (OR) of remission was 1.02 (95%CI=0.63,1.67). In PP analysis, 40% of dual-action episodes ended in remission compared to 32% in single-action episodes. Dual-action episodes had 1.33 times the odds of remission (95%CI=0.55,3.21), however the result was not statistically significant. Non-significant differences were also observed for depressive symptom severity.

Limitations

Missing data was common but was addressed with inverse probability weights.

Conclusions

Results suggest that single-action and dual-action antidepressants are equally effective in PLWHA. Remission was uncommon highlighting the need to identify health service delivery strategies that aid HIV providers in achieving full remission of their patients’ depression.

Introduction

Depression is the most common psychiatric disorder among people living with HIV/AIDS (Nanni et al., 2015). People living with HIV/AIDS (PLWHA) are two to four times as likely to suffer from depression compared to the general population (Kaaya et al., 2013, Nanni et al., 2015, Wendorf and Mosack, 2013). Depression is associated with suboptimal antiretroviral treatment (ART) adherence, accelerated HIV disease progression, decreased quality of life, increased morbidity and premature mortality (Nanni et al., 2015).

Given the consequences of depression for PLWHA, depression treatment is extremely important. One common treatment approach is antidepressant medication. Several antidepressants with different pharmacological properties are considered appropriate for 1st line treatment in PLWHA. Currently selective-serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressants to PLWHA (Freudenreich et al., 2010). SSRIs (e.g. citalopram) are considered to be single–action antidepressants because they impact only one neurotransmitter known as serotonin (Delgado, 2009, Rakesh, 2004). Dual-action antidepressants are another category of medications used as treatment for depression in PLWHA. Dual-action antidepressants differ from those with single-action in that they impact two neurotransmitters thought to be associated with depression (i.e. serotonin, norepinephrine, or dopamine) at the same time (Rakesh, 2004). Examples of dual-action antidepressants considered appropriate for PLWHA include serotonin-norepinephrine reuptake inhibitors (e.g. venlafaxine), bupropion and mirtazapine (Adams et al., 2012).

Randomized controlled trials have demonstrated that antidepressants have high levels of efficacy in PLWHA (Hill and Lee, 2013, Himelhoch and Medoff, 2005, Pence et al., 2012). However, there is limited literature that has compared the effectiveness of the different antidepressants currently used to treat PLWHA for depression. In fact we found only one study that compared a single-action and dual-action antidepressant commonly used today among PLWHA (Patel, 2013). This randomized open label eight-week trial compared mirtazapine (dual-action) to escitalopram (single-action) in a sample of seventy HIV positive patients. While remission and response rates did not differ statistically, the median Hamilton Rating Scale for Depression (HAM-D) score at eight weeks was significantly lower for mirtazapine (median=4) compared to escitalopram (median=12) with a p-value of <0.001.

In contrast, substantial effort has been given to comparing effectiveness between antidepressants among populations without HIV infection (Bauer et al., 2009, Bradley and Lenox-Smith, 2013, Delgado, 2009, Gartlehner et al., 2011, Grunebaum et al., 2013, Rakesh, 2004, Richelson, 2013). These studies are based on the hypothesis that broader spectrum antidepressants with dual action may be more effective than those with single action because depression can arise out of dysfunction along multiple neurotransmitters pathways (Delgado, 2009, Rakesh, 2004). While earlier studies revealed potential advantages for dual-action antidepressants (Bauer et al., 2009, Delgado, 2009, Rakesh, 2004), results from a more recent meta-analysis analysis concluded that there were no significant differences according to type of medication (Gartlehner et al., 2011). However, there was a paucity of evidence specific to PLWHA contained in the meta-analysis, therefore caution is warranted when generalizing the conclusion to those with HIV-infection.

In fact, more nuanced findings from general population studies suggests that further investigation of the comparative effectiveness of dual-vs. single-action antidepressants is warranted in PLWHA. First, mirtazapine is known to have a faster onset of action compared to single-action SSRIs (Gartlehner et al., 2011). While timely alleviation of depressive symptoms is important for all people with depression, it is especially salient to PLWHA given the negative HIV/AIDS related health consequences associated with this psychiatric condition. Secondly, bupropion has a lower risk of sexual side effects compared to single-action SSRIs which may lead to better antidepressant treatment adherence (Gartlehner et al., 2011) and therefore better response. PLWHA have been shown to be at higher risk of sexual dysfunction, independent of antidepressant exposure (Bouhnik et al., 2008), therefore in order to avoid additional exascerbation of this problem, bupropion may be more advantageous in the context of HIV infection. Finally, in a systematic review conducted in 2013, authors found sufficient evidence to conclude that SNRIs may have greater efficacy than SSRIs for more severe cases of depression. (Bradley and Lenox-Smith, 2013) These findings are relevant to PLWHA given depression in HIV/AIDS is typically chronic and often accompanied by additional psychiatric diagnoses (e.g. anxiety, substance use disorder), which in turn lends itself to greater severity in depressive symptomology.

Despite the potential advantages from dual-action antidepressants for PLWHA highlighted above, a significant gap remains in research comparing antidepressants in PLWHA. To address this gap, we compared the effectiveness of dual-action and single-action antidepressants for achieving remission from depression among PLWHA. We also assessed comparative effectiveness for depression symptom severity. Results from this study have the potential to generate much needed comparative evidence that can reduce uncertainty for a physician when choosing an antidepressant to treat depression in PLWHA. We hypothesized that dual-action antidepressants would be more effective than single-action antidepressants for achieving remission and reducing depression symptoms.