Table 2.
Representative longer-term studies of stimulants in adults with attention-deficit/hyperactivity disorder†.
| Study (year) | n | Design | Medication | Duration | Total dose mean and/or range | Outcome | Comments | Ref. |
|---|---|---|---|---|---|---|---|---|
| Levin et al. (1998) | 12 | Open | MPH SR | 12 weeks | 68 mg/day 40–80 mg/day |
Improved ADHD and cocaine use | Cocaine abusers, eight out of 12 completed; no abuse of MPH | [65] |
| Horrigan et al. (2000) | 24 | Open | AMP salts | 16 weeks | 11 mg/day | 54% response rate on CGI | Low doses used; retrospectively analyzed | [66] |
| Schubiner et al. (2002) | 48 | Double-blind, placebo parallel | MPH | 12 weeks | 79 mg/day 30–90 mg/day |
77% response rate on global improvement scale (21% placebo) | Comorbid cocaine dependence; CBT for both arms | [67] |
| Weisler et al. (2005); Biederman et al. (2005) | 223 | Open | MAS ER | ≤24 months | 20, 40 and 60 mg/day | ADHD RS improved for all (p < 0.001) | AEs were mild to moderate, minimal cardiovascular effects; extension of double-blind study | [68,69] |
| Weiss et al. (2006) | 98 | Double-blind, placebo factorial | Paroxetine and/or d-AMP | 20 weeks | Paroxetine (10, 20, 30 and 40 mg/day) d-AMP (5,10, 15 and 20 mg/day) |
64% response rate to d-AMP, 44% response rate to paroxetine/d-AMP, 17% response rate to paroxetine (16% placebo) | Patients who received both d-AMP and paroxetine had more severe AEs, but did not show greater improvement overall than patients treated with one medication | [70] |
| Levin et al. (2007) | 106 | Double-blind, placebo parallel | MPH | 14 weeks | 40 mg/day 10–60 mg/day |
47% response rate on AARS (55% placebo) | SUD study; toxicology revealed decreased probability of cocaine in urine for MPH vs placebo (p = 0.001) | [71] |
| Spencer et al. (2008) | 274 | Double-blind, placebo parallel | Triple bead AMP salts (MAS) | 5 weeks (Phase I); 2 weeks (Phase II); 7 weeks (Phase III) | 13, 25, 38, 50, 63 or 75 mg/day after dose optimization | 52% response rate on CGI (21% placebo) | Mild-to-moderate AEs of insomnia, dry mouth, decreased appetite, headache, weight loss; improved quality of life >12-h duration | [33] |
| Rösler et al. (2009) | 359 | Double blind, placebo parallel | MPH ER | 6 months | 41 mg/day | 61% response rate (42% placebo) | Relatively low doses used; increased heart rate among MPH ER group | [72] |
| Weisler et al. (2009); Ginsberg et al. (2011) | 349 | Open | LDX | 12 months | 30, 50 or 70 mg/day | 84% improvement on CGI | Most AEs were mild to moderate in severity | [73,74] |
| Adler et al. (2009) | 170‡ | Open | d-MPH ER | 6 months | 20–40 mg/day | 95% response rate on CGI | Open-label extension of Spencer et al. [32] | [75] |
| Bejerot et al. (2010) | 133 | Open | MPH d-AMP |
6–9-month follow-up | 49 mg/day 18–90 mg/day 28 mg/day 15–70 mg/day |
80% response rate | 66 of 133 discontinued (38% of which before the 6–9-month time point) | [76] |
| Marchant et al. (2010) | 34 | Open | OROS MPH | 6 months | 60 mg/day | 85% response rate on CGI | Followed double-blind crossover phase; all 34 included for safety phase | [77] |
| Wender et al. (2010) | 78 | Open | MPH | 12 months | 60 mg/day 30–100 mg/day |
94% response rate on CGI | Participants who improved on MPH IR double-blind phase entered the 12-month, open-label trial | [64] |
| Konstenius et al. (2010) | 24 | Double-blind, placebo parallel | OROS MPH | 13 weeks | 18–72 mg/day | 84% retention in treatment completers (59% placebo) | Both groups reduced ADHD Sxs; no difference found between groups in craving for AMP | [78] |
| Biederman et al. (2010) | 227 | Three-phase, double-blind, placebo parallel | OROS MPH | 6 weeks (Phase I); 24 weeks (Phase II); 4 weeks (Phase III) | 78 mg/day OROS MPH at Phase I end point (mean) | 62% response rate on CGI and AISRS (37% placebo) | Results include Phase I end point response rates only | [79] |
| Total | ||||||||
| n = 15 | n = 1989 12–359 (range) |
Double blind: 7 Open: 8 |
MPH: 10 AMP: 5 LDX: 1 |
12 weeks – 12 months | 10–100 mg/day MPH 5–75 mg/day AMP 30–70mg/day LDX |
Long term efficacy of MPH and AMP documented | AEs mild-to-moderate in severity | |
Response rate refers to subject reporting much-to-very-much improved (i.e., by CGI) or clinically significant reduction in symptoms on ADHD rating scales.
†
At least 12 weeks.
‡
Subjects not included in total n.
AARS: Adult Attention-Deficit/Hyperactivity Disorder Rating Scale; ADHD: Attention-deficit/hyperactivity disorder; AE: Adverse event; AISRS: ADHD Investigator Symptom Report Scale; AMP: Amphetamine; CBT: Cognitive behavioral therapy; CGI: Clinical Global Impression; d-AMP: Dexamphetamine; d-MPH: Dexmethylphenidate; Dx: Diagnosis; ER: Extended release; IR: Immediate release; LDX: dimesylate; MAS: Mixed amphetamine salt; MAS ER: Mixed amphetamine salt extended release; MPH: Methylphenidate; OROS MPH: Osmotic-release oral system methylphenidate; RS: release; SUD: Substance use disorder.