Design
MEMAP is a two-arm, randomised, placebo-controlled, double-blind, parallel, multi-centre phase IIIb exploratory study to evaluate the efficacy and safety of methylphenidate in the initial treatment of acute mania in patients with bipolar affective disorders. After being screened for eligibility and signing the informed consent (day -2 or day -1), patients will be randomised to either 2.5 day treatment with methylphenidate BID or placebo BID at a 1:1 ratio (day -1/day 0). Medication will be administered at 10.00 and 15.00 h on day 0 (15 mg methylphenidate or placebo BID), at 09.00 and 15.00 h on day 1 (20 mg methylphenidate or placebo BID), and at 09.00 h on day 2 (20 mg methylphenidate or placebo). EEG should be conducted prior to first medication and 2 h after the morning dose on day 2. Manic symptoms will be assessed using the YMRS. YMRS will be scored at baseline and 2 h after the morning dose on every day. In addition, the CGI-BP and PANSS-EC will be scored. Furthermore, movements will be recorded using actigraphy and a cognitive test (SCIP) [45] will be performed. The schedule of study assessments is described in detail in Table 1.
Table 1  Schedule of study assessments  *day -1 after informed consent.
Number of ‘X’ represents number of assessments (X* 15 mg methylphenidate vs. placebo, X** 20 mg methylphenidate vs. placebo).  Pre-existing medication for treatment of bipolar disorder that has been stable for at least 4 weeks including benzodiazepines, lithium, anticonvulsants or antipsychotics will be continued in the same dose. Only patients receiving up to 2 such drugs are eligible for study participation. During screening, the (additional) use of up to 3 mg/day lorazepam or alprazolam is allowed. The treatment period is 2.5 days. There will be two post treatment visits at day 3 and 9.