Table 2 Summary result of clinical trials assessing the efficacy of SNRIs in ADHD
Autor, year | Medication administration routinea | Comparator arm | Trial duration | Resultb | Side effect | Tolerabilityc |
|---|---|---|---|---|---|---|
Venlafaxine | ||||||
Olvera et al. 1996 [36] | • For < 40 kg: 50 mg daily • For > 40 kg: 75 mg daily | Pre- and post-treatment | 5 weeks | • Significant improvements in the CPRS were observed • There were no statistically significant effects on the CPT • Seven out of the original 16 subjects (44%) responded positively to venlafaxine, based on the CPRS. These responders displayed a decrease of at least 1 SD from their baseline | • 50% drowsiness • 37% nausea • 31% irritability • 31% worsening of hyperactivity • There was no evidence of akathisia among these patients and no appreciable effect on blood pressure or heart rate | 10% |
Findling et al. 2007 [37] | • First two weeks: 37.5 mg daily • Second two weeks: 75 mg daily • Third two weeks: 150 mg daily | Pre- and post-treatment | 6 weeks | • Parent ARS-IV total scores indicated a significant improvement in this measure over baseline for the total score, inattentive, and hyperactive-impulsive subscales (all p < 0.001) • The total score was significantly improved over the baseline on the teacher version of the ARS-IV (p < 0.03) • But the improvement in hyperactivity-impulsivity symptoms did not reach statistical significance (p < 0.06) | • 31% headache and nausea • There were no statistically significant changes in mean BP or pulse rate | 0.2% |
Hashemian and Nazemian 2015 [38] | • 0.5 mg/kg in the first week and 0.1 mg/kg were added every week to reach 1.4 mg/kg in the 10th week | Pre- and post-treatment | 10 weeks | Each group had significant effects by the intervention (p < 0.05), but the difference between the two groups (F = 0.199, sig = 0.659) was not significant in this regard (p > 0.05) | - | – |
• Bupropion: • First week: 1.4 mg/kg • 0.51 mg/kg was added weekly to reach 6 mg/kg in the 10th week | ||||||
Zarinara et al., 2010 [39] | • 50 mg/day for < 30 kg • 75 mg/day for > 30 kg | Pre- and post-treatment | 6 weeks | A significant effect of both protocols on the Parent ARS scores (p < 0.001) was observed. The differences between the two protocols were not significant at the endpoint (p = 0.17) | • 26% abdominal pain • 16% restlessness • 21% nausea and vomiting • 26% somnolence | – |
Methylphenidate: • 20 mg/day for < 30 kg • 30 mg/day for > 30 kg | ||||||
Amiri et al. 2012 [43] | • Week one and two: 75 mg OD • Week three and four: 75 mg BD • Week five and six: 75 mg TDS | Placebo | 6 weeks | Analysis revealed a significant decrease in ADHD symptoms, as measured by total score, by both subscales and the ADHD index, in both the venlafaxine group (p < 0.001) and the placebo group (p < 0.001). However, the difference between the two groups for the decrease in the inattentive symptom subscale (p = 0.539), the hyperactive/impulsive symptoms subscale (p = 0.172), the ADHD symptoms total score (p = 0.268), and the ADHD index (p = 0.188) did not reach statistical significance | • No serious adverse effects were reported during the trial • There was no significant change in weight • The same was true for changes in systolic and diastolic blood pressure • 50% Dry mouth • Some participants had decreased appetite, insomnia, nausea, vertigo, constipation, anxiety, stomachache, and irritability | 5% |
Pre- and post-treatment | ||||||
Mukaddes and Abali 2004 [40] | • Venlafaxine was initiated at a dose of 18.75 mg/day OD • The dose was flexibly titrated up to 56.25 mg/day (until unwanted effects occurred) | Pre- and post-treatment | 6 weeks | • There was a statistically significant improvement in the mean total score of the Conner 10-item parent index from baseline to endpoint • Also, the CGI severity item showed a statistically significant change from baseline to endpoint (p < 0.05) | • 15% somnolence • 15% stomach ache • 7% headache • 7% behavioral activation • 23% sedation only at higher doses (56.25 mg/day) | 0% |
Hornig-Rohan & Amsterdam, 2002 [41] | • Venlafaxine 100–500 mg daily (mean 329 ± 150 mg) | Stimulant (dextroamphetamine or methylphenidate) | 8 to 12 weeks | • Four of five (80%) venlafaxine-treated patients responded partially or completely to MDD and ADD symptoms • In contrast, only two of six patients (33%) treated with stimulant monotherapy showed a partial response to both MDD and ADD symptoms | • Mild nausea • Mild insomnia | – |
Adler et al., 1995 [45] | • The starting dose was 25–37.5 mg daily • Raised weekly to 225 mg per day | Pre- and post-treatment | 8 weeks | • WURS rating scale decreased by an average of 48% at the end of the treatment | • Sedation • Agitation • Nausea | 34% |
Findling et al. 1996 [42] | • 37.5 mg BD at first. If each subject had any ADHD symptoms after 4 weeks, then the dose was raised to 75 mg BD | Pre- and post-treatment | 8 weeks | • There was an overall significant effect for inattention, hyperactivity-impulsivity, and total ADHD scores • CGI scores showed a consistent decline over the study period | • 40% nausea • 30% constipation • 30% somnolence • 30% anxiety | 11% |
Hedges et al. 1995 [44] | • Started with 18.75 mg per day. The dose was increased until either a response or a side effect happened | Pre- and post-treatment | 4 weeks (longer but data are reported for 4 weeks) | • Based on the CGI score, 61% of patients had some response, with 50% moderately or very much improved and 11% mildly improved | • 39% had significant side effects • 50% nausea • 33% fatigue • 17% lowered libido • 17% gas and abdominal pain | 39% |
Duloxetine | ||||||
Bilodeau et al. 2014 [33] | • Duloxetine 60 mg OD | Placebo | 6 weeks | • The duloxetine group showed significantly lower symptom severity than the placebo group (24.86% reduction in DSM-IV ADHD Symptoms Total) | • 40% xerostomia, increased anxiety, nausea, and dizziness • All participants reported that their symptoms resolved, except 1 participant who reported reduced appetite at the study conclusion | 40% |
Mahmoudi‐Gharaei et al. 2011 [34] | • First week: 30 mg/day OD • From week 2 to the end of the study: 60 mg/day | Pre- and post-treatment | 6 weeks | • A significant decrease in all four subscales of CPRS‐R (oppositionality, inattention, hyperactivity, and ADHD index) was observed at the end of the study | • 46% decreased appetite • 30% dry mouth • 23% insomnia, headache, nausea, somnolence, anxiety, and nervousness • The side effects were mild or moderate in severity and did not necessitate dose reduction or any other intervention | 17% |
Dodangi et al. 2015 [35] | • First week: 15 mg/day OD • The next 5 weeks: 30 mg/day OD | Pre- and post-treatment | 6 weeks | • Data analysis showed that the decrease in the overall Conners score and its subscales (except for the inattentiveness subscale) • The attention-deficit hyperactivity subscale showed a significant decrease compared with baseline values from the fourth week afterward • The overall reduction in the Conners scale compared with the baseline values in the second, fourth, and sixth weeks was 22%, 33%, and 33%, respectively | • No weight changes • Changes in blood pressure, pulse, electrocardiography, and laboratory parameters, including cell blood count, fasting blood sugar, thyroid function tests, blood urea nitrogen, creatinine, liver function tests, and electrolytes, were insignificant • 7% were excluded because of severe GI problems • 14% anorexia • 7% mild nausea | 7% |