Table 2.
Summary of clinical trials using indirect and direct dopaminergic agonists to improve poststroke motor recovery.
| Study | Number of patients | Time from stroke | Drug dosage | Additional rehabilitation | Outcome |
|---|---|---|---|---|---|
| Acler et al., 2009 | 10 | 10–48 months poststroke | Crossover study design, 100 mg L-DOPA daily or placebo daily for 5 weeks, followed by 2 months of washout and the other condition (single blind) | No physiotherapy | L-DOPA improved walking speeds (10 m walking test), manual dexterity with the paretic hand (9-hole peg test), and no change on the RMA. Increase in cortical silent period as detected by TMS, no changes were seen in the placebo group |
| Cramer et al., 2009 | 33 | 1–12 months poststroke | Daily doses of ropinirole or placebo for 9 weeks, goal to work up to 3 mg/kg with doses adjusted weekly | Physiotherapy given twice a week about 1 h after drug intake from weeks 6 to 9, patients expected to complete 30 min/day of physiotherapy at home after taking medication | No differences were apparent between treatment groups on gait velocity, gait endurance, arm, or leg FM score or BI |
| Crisostomo et al., 1988 | 8 | ≤10 days poststroke | A single 10 mg dose of AMPH | 45 min of physiotherapy within 3 h of drug | Statistically significant improvement of the AMPH group above the level of the placebo group by the FM scale |
| Floel et al., 2005 | 9 | >1 year poststroke | Crossover trial design, with a single dose of 100 mg L-DOPA (with carbidopa) and placebo separated by 24 h | Task specific training 60 min following drug or placebo administration | Improved motor-learning on a TMS stimulated thumb movement task |
| Gladstone et al., 2006 | 71 stratified by hemiparesis severity | 5–10 days poststroke | 10 mg AMPH or placebo | Ten 1-h sessions of physiotherapy given after drug administration | No significant difference in improvement above the level of placebo on the FM scale |
| Grade et al., 1998 | 21 | Sub-acute stage, specifics unclear | 3 weeks of daily MPH, starting at 5 mg and increasing to 30 mg or placebo | Physiotherapy | Significant improvement of the MPH group on the motor portion of the FIM |
| Kakuda et al., 2011 | 5 | 18–143 months poststroke | 1 week of prior 100 mg L-DOPA, 15 days of inpatient protocol with continuing L-DOPA and 4 weeks L-DOPA after inpatient protocol, no placebo group | 2 daily session of 30 min low frequency TMS applied to the contralateral hemisphere, 1 h of intensive occupational therapy and 1 h of self-exercise during the inpatient protocol | All patients showed improvement in motor function as measured by the FM scale and the Wolf Motor Scale |
| Lokk et al., 2011 | 78 | 15–180 days poststroke | 125 mg L-DOPA, 20 mg MPH, 125 mg L-DOPA and 10 mg MPH or placebo, 5 days a week for 3 weeks | Physiotherapy 1 h after drug administration | Significantly better improvement on BI and NIHSS for all drug groups as compared to placebo, but not on the FM scale, at the 6 month follow-up |
| Martinsson and Wahlgren, 2003 | 45 | ≤72 h poststroke | 2.5, 5, or 10 mg dose of D-AMPH given orally twice a day, or placebo for 5 days | No additional physiotherapy | Significantly better improvement on LMAC motor function score and AI motor score and SSS-68 at day 7 follow-up in AMPH group, no difference at 1 or 3 months |
| Masihuzzaman et al., 2011 (abstract only) | 97 | Unspecified | 125 mg L-DOPA or placebo, frequency unspecified | Physiotherapy with drug administration | L-DOPA group had significantly greater increase in RMA as compared to placebo |
| Mazagri et al., 1995 (abstract only, discussed in Long and Young, 2003) | 25 | ≤72 h poststroke | A single 10 mg dose of D-AMPH or placebo | Physiotherapy | No improvement of AMPH group above the level of placebo group at 48 h or 3 months after treatment in FM scale, BI, and CNS |
| Platz et al., 2005 | 26 | An average of 5.6 weeks poststroke | 10 mg D-AMPH or placebo twice a week for 3 weeks | Arm training 2 h after drug administration | D-AMPH group did not improve above the level of placebo group during or after training, or at 1 year follow-up in TEMPA task (an ADL measure), an aiming task, a finger tapping task and time to walk 10 m |
| Reding and Borucki, 1995 (abstract only, discussed in Long and Young, 2003) | 21 | <1 month poststroke | 10 mg D-AMPH for 14 days followed by 5 mg D-AMPH for 3 days or placebo | No physiotherapy provided by the study | No benefit of AMPH group as compared to placebo on the FM scale or the BI |
| Restemeyer et al., 2007 | 10 | >6 months poststroke | Crossover trial design, single dose of 100 mg L-DOPA (with carbidopa and domperidone) and placebo | 1 h of physiotherapy after drug administration | No benefit of L-dopa on the 9 hole peg test, grip strength, Action Research Arm Test, or excitability as measured by TMS |
| Rösser et al., 2008 | 18 | Patients in chronic stage, a mean of 3.3 years poststroke | Crossover study design, comparing 3 doses of 100 mg L-dopa (with carbidopa) or placebo | Drug administration followed by 1 session of procedural motor learning | Better procedural motor learning in the L-DOPA group on a serial reaction time task with a probabilistic sequence in the paretic hand |
| Scheidtmann et al., 2001 | 53 | Between 3 and 6 months poststroke | 100 mg L-DOPA (with carbidopa) or placebo daily for 3 weeks | Physiotherapy daily (with drug) for 3 weeks followed by 3 weeks of only physiotherapy (Monday to Friday) | Significant improvement of the L-dopa group as compared to the placebo group as measured by the RMA |
| Schuster et al., 2011 | 16 | 14–60 days poststroke | 10 mg D-AMPH or placebo orally twice a week for 5 weeks | Physiotherapy given after each drug administration | Significantly better improvement on ADL and the arm subscale of the CMSA compared to placebo |
| Sonde and Lökk, 2007 | 25 | 5–10 days poststroke | 10 doses 20 mg of d-AMPH over 2 weeks or 10 mg D-AMPH and 50 mg L-DOPA or 100 mg L-DOPA or placebo | Physiotherapy after drug intake | Did not see benefit above the level of placebo on the FM scale or BI for any drug condition |
| Sonde et al., 2001 | 39 | 5–10 days poststroke | 10 mg D,L-AMPH or placebo given twice a week for 5 weeks | Physiotherapy given 1 h after each drug administration | AMPH group did not show improvement above the level of placebo on the FM or BI |
| Treig et al., 2003 | 24 | ≤6 weeks poststroke | 10 sessions of 10 mg D-AMPH or placebo every 4th day | Physical therapy within 1 h of drug intake | No benefit of AMPH above placebo on the BI or the RMA over course of treatment or at 90 day follow-up |
| Vachalathiti et al., 2001 (abstract only, discussed in Long and Young, 2003) | 27 | An average of 5.7 days poststroke | 10 mg D-AMPH daily for 7 days | Not stated | No difference between AMPH and control groups on the FM scale and the BI |
| Walker-Batson et al., 1995 | 10 | Between 16 and 30 days poststroke | 10 mg D-AMPH orally every 4th day for 10 sessions (single blind) | Physiotherapy after drug administration | Drug group had significant benefit as compared to placebo at 1 week and 1 year from treatment conclusion as measured by the FM scale |
| Wang et al., 2014 | 9 | 7–30 days poststroke | One time dose of 20 mg liquid MPH, orally or placebo | Transcranial direct current stimulation (tDCS) or sham tDCS | All groups showed improvement on the Perdue Pegboard test, combination MPH and tDCS showed improvement above the level of either treatment alone |
The above table summarizes the studies discussed in the text using amphetamine (AMPH), levodopa (L-DOPA), methylphenidate (MPH) and ropinirole. The following short forms have been used to indicate outcome measures: RMA, Rivermead Motor Assessment; FIM, Functional Independence Measure; BI, Barthel Index; FM, Fugl-Meyer; NIHSS, National Institute of Health Stroke Scale; ADL, Activities of Daily Living; CMSA, Chedoke-McMaster Stroke Assessment; CNS, Canadian Neurological Scale; AI, Activity Index; SSS68, Scandinavian Stroke Scale 68; LMAC, Lindmark Motor Assessment Chart; and the TEMPA task, Test Évaluant les Membres Supérieurs des Personnes Agées, a test of upper extremity function in the elderly.