Table 1 Summary of clinical evidence
From: The renin–angiotensin system: a possible new target for depression
Studies | Findings | Conclusion | Limitations | |
|---|---|---|---|---|
MDD | ||||
Zubenko et al., 1984 | Case report of mood-elevating effect of captopril in three MDD patients | 3 patients: 72-year-old man with CHF 44-year-old woman with HT 67-year-old man with CHF | Mood elevation of the 3 cases with captopril | 3rd case developed psychotic symptoms |
Deicken, 1986 | Case report of captopril treatment of MDD | 52-year-old man with HT and D | Improvement of MDD symptoms with captopril | Â |
Germain & Chouinard, 1988 | Case report of treatment of MDD with captopril | 41-year-old man with D and posterior diagnosis of HT | Total remission of the MDD episode with captopril | Â |
Hertzman et al., 2005 | Collection of case reports of lisinopril augmenting antidepressant response (9 MDD + 1 BD) | Mood elevation of MDD and stabilised mood of the BD patient with lisonopril in patients already on antidepressants or MSs All patients being treated for HT | Improved mood with a combination of antidepressants and lisinopril |  |
Rathmann et al., 1999 | Case-control study of 972 diabetic patients | OR for MDD: CCB: OR 2.2 (95% CI: 1.2–4.2) BB: OR 2.6 (95% CI: 1.1–7.0) ACEI: OR 1.3 (95% CI: 0.8–2.2) | ACEI associated with reduced risk of MDD | Screening for MDD made by general practitioners |
Williams et al., 2016 | Case-control study of a 5-year cohort of 961 men with osteoporosis | Exposure to ACEIs yields reduced risk of MDD (OR: 0.15, 95% CI: 0.04–0.51, P = 0.003) | ACE inhibitors were associated with a reduced likelihood for MD onset | Recall bias, unrecognised confounding and limited generalisability |
Boal et al., 2016 | 5-year cohort of 144,660 patients | ACEI/ARB: 53% decreased risk of MD admissions CCB & BB: 2-fold increased risk of MD admissions TZ & NT did not attain statistical significance | ACEI/ARB therapy had a neutral effect (or reduced risk) on MDs | Results do not include milder levels of MDs treated in the community |
Negative findings in MDD | ||||
Habra et al., 2010 | RCT of citalopram in 284 patients with MDD and coronary disease | Use of ACEIs associated with mean HAMD response of 1.36 versus 6.42 for non-ACEI use | ACEI use predicted worse response to antidepressant | Bias for more severe coronary disease |
Mood effects in non-depressed population | ||||
Cohen et al., 1984 | Case report of mood elation with enalapril | Produced elation in normal volunteers (33% controls and 27% HT subjects) | Mood elation effect | Â |
Croog et al., 1986 | RCT on the quality of life of captopril versus methyldopa versus propranolol in 626 male HT patients for 24 weeks | Captopril: fewer side effects, and better scores for work performance, visual–motor functioning, and measures of life satisfaction versus methyldopa (P < 0.05 to < 0.01) Captopril: fewer side effects, less sexual dysfunction and greater improvement of measures of general well-being versus propranolol (P < 0.05 to < 0.01) | Captopril group had better scores in tests of general well-being |  |
Testa et al., 1993 | RCT on the quality of life of captopril versus enalapril in 379 HT men for 24 weeks | Captopril: more favourable reports of overall quality of life, general perceived health, vitality, health status, sleep, emotional control (P < 0.05) | The centrally acting ACEI (captopril) showed superior quality of life reports despite equal anti-HT response |  |
Johansen et al., 2012 | HUNT study (Norway) 55,472 HT patients | OR for depressive symptoms: ACEI: OR 0.54, 95% CI 0.28–1.08 BB: OR 1.20, 95% CI 0.78–1.83 CCBs: OR 1.04, 95% CI 0.70–1.53 | Depressive symptoms were reduced in ACEI, compared to BB and CCB group | Self-reported data |
Pavlatou et al., 2008 | Open-label study of candesartan in 17 diabetic patients for ≥ 3 months | Significant improvement in interpersonal sensitivity (P = 0.027) and depression scores (P = 0.026) | Candesartan (an ARB) improves affect | No control group |
Negative findings in mood effects in non-depressed population | ||||
Callender et al., 1983 | Double-blind placebo-controlled crossover trial with captopril in 8 HT patients for 6Â weeks | Mood was slightly lower during captopril administration | No evidence of mood effects of captopril during the trial | Small sample and duration of study |
Deary et al., 1991 | Double-blind crossover trial of atenolol and captopril in 18 HT patients for 12 weeks (6 weeks each drug) | Patients reported feeling less anxious during treatment with atenolol (a BB) (P = 0.02). | A BB was superior to an ACEI in self-reported anxiety | BBs are known to have an effect in somatic anxiety |
Omvik et al., 1993 | RCT on the quality of life of amlodipine versus enalapril in 461 HT patients for 50Â weeks | Indices on quality of life were unchanged or increased in both groups | No difference between a CCB and an ACEI in quality of life | Â |
Fletcher et al., 1992 | RCT on the quality of life of cilazapril versus atenolol versus nifedipine in 540 HT patients for 6Â months | Little difference between quality of life measures in the cilazapril and atenolol groups. Both superior to nifedipine | No significant differences in quality of life observed between an ACEI and a BB during the trial. Both were superior to a CCB. | More nifedipine dropouts (17%) compared with atenolol (8%) and cilazapril (5%) |
Weir et al., 1996 | RCT on the quality of life of losartan versus nifedipine in 223 HT patients for 12Â weeks | No significant differences in quality of life reports between groups | No significant differences in quality of life were observed between an ACEI and a CCB | Nifedipine had significantly more dropouts (12%) than losartan (5%) |