Methylphenidate for the Treatment of Acute Mania

• EEG-vigilance as assessed by the Vigilanz Algorhithm Leipzig (VIGALL) [ Time Frame: after 2.5 days of treatment ] [ Designated as safety issue: No ]
• movements as assessed by actimetry [ Time Frame: after 2.5 days of treatment ] [ Designated as safety issue: No ]
• cognitive performance as assesd with the Screen for Cognitive Impairment in Psychiatry (SCIP) [ Time Frame: after 2.5 days of treatment ] [ Designated as safety issue: No ]

This study aims at evaluating the efficacy and safety of methylphenidate in the initial treatment of acute mania in patients with bipolar affective disorders.

Mania can be regarded as an autoregulatory mechanism to enhance unstable vigilance. There is increasing evidence that psychostimulants that increase vigilance may be effective in treating mania. However, controlled studies are lacking.

This 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.

• Drug: methylphenidate
  tablets for oral use
• Drug: Placebo
  tablets for oral use

• Active Comparator: methylphenidate
  Intervention: Drug: methylphenidate
• Placebo Comparator: placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

1. Inpatients
2. Written informed consent by patients who are competent to consent to study participation.
3. Diagnosis: manic episode according to the International Classification of Diseases 10th Revision (ICD-10): F30.0, F30.1, F31.0 or F31.1
4. Male or female of at least 18 years of age
5. YMRS total score ≥ 20 and ≤ 45 points
6. Body mass index (BMI) > 17
7. Patients must be able to swallow tablets (study drug).

Exclusion Criteria:

1. Any other current major psychiatric ICD-10 disorder is an exclusion criterion except for the following F90, F17.1, F17.2, F40-F59, F60-F69
2. Contraindications for treatment with methylphenidate except as noted otherwise
3. Serious non-psychiatric disease, that may interfere with the objectives of the study or with the safety or compliance of the subject, as judged by the investigator
4. Oral administration of monoaminooxidase (MAO)-inhibitors within two weeks, fluoxetine within 6 weeks and of any other antidepressant or primarily psychotropic substance except for those specified below within one week before study entry.
5. Stable treatment with mood stabilisers including lithium, anticonvulsants (e.g. valproate, carbamazepine) or antipsychotics (e.g. risperidone, olanzapine) or benzodiazepines is NOT an exclusion criterion and will be continued; however, patients receiving more than 2 of these substances are NOT eligible for inclusion
6. Medical history of other disorders of CNS including tics or dyskinesia
7. Medical history of cardiovascular diseases, severe hypertension, glaucoma, hyperfunction of the thyroid
8. Patients with congenital or acquired long QT syndrome, or with a familiy history of QT prolongation, sudden cardiac death or other significant inherited cardiac disorders (e.g. family history of hypertrophic cardiomyopathy).
9. History of Electroconvulsive therapy within the last 3 month
10. Known alcohol and drug addiction or abuse, except for patients with abstinence > 3 month. Patients with sporadic abuse of cannabis (products) will not be excluded from the study. That is even true with a positive Tetrahydrocannabinol (THC) screen in urine.
11. Pregnant or nursing woman
12. Concomitant participation in other clinical trials or participation during the 30 days prior to screening
13. Prior participation in this study
14. Suicidality