Please select the eligibility criteria that correspond to the clinical trial below.
Title: Enhanced Motor Recovery Using Serotonergic Agents in Stroke
Brief Summary: The information derived from this study will be critical to establishing appropriate rehabilitative interventions post-stroke. In particular, traditional use of pharmacological agents to alter motor function post-stroke is directed primarily at reducing the "positive" signs following upper motor neuron lesion, in particular spasticity, or enhanced, velocity-dependent stretch reflex responses to imposed stretch. While pharmacological management of spasticity certainly suppresses clinical and quantitative measures of hypertonia, there is little improvement in functional performance. In contrast, preliminary data on the administration of 5HT agents following neurological injury indicates an increase in motor performance (Pariente 2001) and recovery (Dam 1996), despite an increase in spastic motor activity (Stolp-Smith 1999; see Preliminary Data below). Understanding methods to maximize function following stroke despite potential, short-term increases in spastic motor activity may improve therapeutic intervention strategies. The general objective of this study is therefore to:

1. quantify the effects of short-term SSRI administration on voluntary and spastic motor behaviors in individuals with chronic spastic hemiparesis,
2. identify the changes in impairments and functional recovery of walking ability during BWSTT with the presence or absence of SSRIs.


Options:
A: Inclusion Criteria:

* Ischemic infarction within the past 2 years post event that has caused hemiparesis or hemiplegia, as self-reported and/or confirmed by medical record.
* Older than 18 years old.
* Upper extremity weakness defined as a score of \>11 and ≤56 on the arm motor Fugl-Mayer motor scale.
* Minimal pre-stroke disability defined as a score of \<3 in the Modified Rankin Scale.
* Subjects need to be able to follow directions and participate in 2 hours of testing with short breaks.
* Subjects need to be able to provide informed consent.

Exclusion Criteria:

* Any substantial decrease in alertness, language reception, or attention that might interfere with understanding instruction for motor testing
* Excessive pain in any joint of the paretic extremity (not applicable to severe stroke subjects), as self reported
* Contraindications to single pulse TMS (will be used to measure cortical excitability) such as: history of seizures, unexplained loss of consciousness, any metal implants in the head, frequent or severe headaches or neck pain, any other electronic implanted medical devices such as pacemakers, defibrillators, or implant medication pump.
* Patients who have taken fluoxetine in the past 5 weeks.
* Patients taking any other SSRI at the time of enrollment or in the previous month.
* Patients taking any other medication likely to have adverse interaction with SSRIs (all the medications the patient is taking will be carefully reviewed, as noted below in "Monitoring of important drug interactions").
* Active depression on admission to SRH defined by a score of 24 or higher in the Hamilton Depression Rating Scale (HAM-D)
* Concurrent medical condition likely to worsen patient's functional status in the next 6 months such as: cancer, terminal heart, kidney or liver disease, as self-reported and/or confirmed by medical record.
* Pregnancy.
B: Inclusion Criteria:

* unilateral supratentorial stroke
* MMSE \> 22
* \> 6 months stroke duration
* \< 0.9 m/s gait speed overground

Exclusion Criteria:

* lower extremity contracture
* osteoporosis
* Cardiovascular/metabolic/respiratory instability
* previous central/peripheral nerve injury
* concurrent medications interacting with SSRIs
C: Inclusion Criteria:

* Informed consent can only be obtained from a patient who according to the trial investigator is mentally capable of decision-making and who, after having received information and got answers to their questions, wants to participate in the trial.
* Brain imaging is compatible with intra cerebral hemorrhage or ischemic stroke.
* Randomization can be performed between 2 and 15 days after stroke onset and by the research group at the patient's local/emergency hospital.
* Persisting focal neurological deficit is present at the time of randomization severe enough to warrant treatment from the physicians and the patient's and relative's perspective.

Exclusion Criteria:

* Subarachnoidal hemorrhage except where secondary to a primary intracerebral hemorrhage.
* Unlikely to be available for follow up for the next 12 months e.g. no fixed home address.
* Unable to speak Swedish and no close family member available to help with follow up forms.
* Other life threatening illness (e.g. advanced cancer) that will make 12-month survival unlikely.
* History of epileptic seizures.
* History of allergy or contraindications to fluoxetine including: Hepatic impairment (S-ASAT/ALAT \> 3 upper normal limit) and renal impairment (S-Creatinine levels \> 180 micromol/L).
* Pregnant or breastfeeding, women of childbearing age not taking contraception. Minimum contraception is an oral contraceptive. An HCG-test is to be made prior randomization and after the end of trial medication.
* Previous drug overdose or attempted suicide.
* Already enrolled into a CTIMP.
* Current or recent (within the last month) depression requiring treatment with an SSRI antidepressant.

Current use of medications which have serious interactions with fluoxetine Use of any mono-amino-oxidase inhibitor (MAOI) during the last 5 weeks. Co-administration of Fluoxetine and a mono-amino-oxidase inhibitor (MAOI) may result in life threatening interactions. Therefore, patients on MAOI are ineligible for the EFFECTS trial. Also, any patient in need of treatment with a MAOI must stop their trial treatment for at least 5 weeks before commencing the MAOI, or to be treated as in-patients by a psychiatrist.
D: Inclusion Criteria:

* Patients who had an acute intracerebral hemorrhage within the past 10 days causing hemiparesis or hemiplegia
* Fugl-Meyer motor scale (FMMS) scores of 55 or less
* Written informed consent for participation in the trial

Exclusion Criteria:

* Severe post-stroke disability (National Institutes of Health stroke scale \[NIHSS\] score \>20)
* Premorbid disability, evidenced by residual motor deficit from a previous stroke
* Comprehension deficit or severe aphasia
* Previous diagnosis of depression or one of the following:

  * Hospital Anxiety and Depression Scale score ≥11 points
  * Taking antidepressant drugs two weeks before inclusion
* Taking neuroleptic drugs or benzodiazepines two weeks before inclusion
* Other major diseases with life expectancy less than 3 months.

Answer: B