Please select the eligibility criteria that correspond to the clinical trial below.
Title: Establishing the Effect(s) and Safety of Fluoxetine Initiated in the Acute Phase of Stroke
Brief Summary: The purpose of this study is to investigate whether routine administration of fluoxetine 20mg once daily in the 6 months initiated during the acute stroke improves the patient's functional outcome.

EFFECTS is an investigator lead Sweden-based, multicenter, parallel group, double blind placebo controlled trial with broad entry criteria and follow up at 6 and 12 months.

EFFECTS managed to recruit its anticipated numbers of 1,500 participants between 20th October 2014 and 28th June 2019. Data will be unblinded when the 6-months follow-up is completed, and the primary outcome is due to report on May 2020.


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:

* Adults older than 20 years
* Patients with acute stroke (ischemic stroke or cerebral hemorrhage) confirmed by neuroimaging within 21 days after stroke onset
* Patients with hemorrhagic transformation of infarcted tissue will not be included, but if investigators judge the risk of bleeding is small (i.e., reduced amount of blood in follow-up neuroimaging) those patients can be enrolled.
* Patients with MRS ≥ 2 on screening
* Patients without definite history of depression
* Patients who fulfill the following criteria in the K-MADRS test:

The combined score of the 9th question (pessimistic thoughts) and the 10th question (suicidal idea) ≤ 7 The score of the 10th question \< 6

* Patients without serious communication problem
* Patients who agree to participate in this trial

Exclusion Criteria:

* Patients with MRS 0 or 1 on screening
* Patients who have definite history of depression or have taken antidepressants
* Patients who have been diagnosed as having bipolar disorder or other psychiatric disorders
* Patients with severe dementia or aphasia. However, those who have motor aphasia but are still communicable can be enrolled
* Patients who have taken migraine medication on screening or those who are expected to take migraine medication frequently due to severe migraine
* Patients who have strong suicidal idea on screening test or those who express their wish to be treated for depression
* Patients who are considered to be treated for depression by charged physicians
* Patients who need SSRI medication for other reasons
* Patients who have taken antiepileptic drugs on screening
* Patients who have a history of traumatic brain injury, brain tumor, or other brain disease (except stroke) within 30 days prior to screening
* Patients with uncommon causes of stroke (e.g. subarachnoid hemorrhage, venous thrombosis, arteriovenous malformation, or Moyamoya disease)
* Patients with bleeding diathesis, hemophilia, or thrombocytopenia
* Patients with severe concomitant illness (e.g. liver disease, renal disease, malignancy)
* Patients with abnormal blood tests Abnormal LFT (ALT \> 200 or AST \> 200) Anemia (Hb \< 8 mg/dl) or thrombocytopenia (\<100,000/mm3) Renal insufficiency (Cr \> 3.0 mg/dl) or renal failure requiring dialysis Patients with severe heart failure (NYHA class III or IV) NYHA classification for heart failure Class I : patients with no limitation of activities; they suffer no symptoms from Ordinary activities Class II : patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion Class III : patients with marked limitation of activity; they are comfortable only at rest Class IV : patients who should be at complete rest, confined to bed or chair; any activity brings on
* Pregnant or lactating patients
* Patients who are participating in another clinical trial, but those who are participating in the observational study can be enrolled
D: 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.

Answer: D