| Eligibility |
Inclusion Criteria:
- Male or female;
- Aged 18-65 years;
- Willing and able to give informed consent for participation in the study;
- Sufficiently fluent English to understand and complete the tasks;
- Registered with a GP and consents to GP being informed of participation in study;
- Participants need to meet a number of concurrent clinical criteria:
- Current criteria for Major Depressive Disorder [as determined by the Structured
Clinical interview for DSM-V (SCID)];
- Failure within the current depressive episode to respond clinically to at least one
course of antidepressant therapy, each given at a therapeutic dose for at least four
weeks [as determined by use of the MGH Antidepressant Treatment Response Questionnaire
(ATRQ)];
- Currently taking an antidepressant, which must be either a Selective Serotonin
Reuptake Inhibitor (SSRI) - with the exception of fluoxetine, paroxetine or
fluvoxamine - or a Serotonin-norepinephrine reuptake inhibitor (SNRI) ; Participants
currently taking excluded medications can be switched to sertraline or citalopram;
- Participants engaging in sex with a risk of pregnancy must agree to use a highly
effective method of contraception from Screening Visit until 30 days after receiving
study medication treatment, and male participants must not donate sperm.
Exclusion Criteria:
- History of or current DSM-V bipolar disorder, schizophrenia or eating disorders.
Participants who fulfil current criteria for other comorbid disorders may still be
entered into the study, if, in the opinion of the Investigator, the psychiatric
diagnosis will not compromise safety or affect data quality;
- First-degree relative with a diagnosis of Bipolar Disorder type 1;
- Participants currently taking strong cytochrome P450 (CYPs) enzymes inhibitors, such
as fluoxetine, paroxetine or fluvoxamine (in order to avoid drug-drug interactions);
- Participants currently taking psychotropic medications which in the opinion of the
investigator may interfere with the safety of the participant or the scientific
integrity of the study;
- Participants who have previously failed a combination/augmentation therapy (i.e.,
therapy with the combination of two or more pharmacological agents) for the treatment
of depression, which in the opinion of the Investigator may reduce the likelihood of
responding;
- Electroconvulsive therapy for the treatment of the current episode of depression;
- Participants undergoing any form of face-to-face structured psychological treatment
during the study;
- Clinically significant abnormal values for liver function tests, clinical chemistry,
urine drug screen, blood pressure measurement and ECG. A participant with a clinical
abnormality or parameters outside the reference range for the population being studied
may be included only if the Investigator considers that the finding is unlikely to
introduce additional risk factors and will not interfere with the study procedures;
- History of stimulant abuse (lifetime; e.g. amphetamine, cocaine), or of alcohol abuse
within one year or of alcohol dependence within the lifetime;
- History of, or current medical conditions which in the opinion of the investigator may
interfere with the safety of the participant or the scientific integrity of the study,
including epilepsy/seizures, brain injury, severe hepatic or renal disease, severe
gastro-intestinal problems, Central Nervous System (CNS) tumors, severe neurological
problems (like Parkinson's Disease; blackouts requiring hospitalisation);
- Clinically significant risk of suicide;
- Current pregnancy (as determined by urine pregnancy test taken during Screening and
First Dose Visits), breastfeeding or planning a pregnancy during the course of the
study;
- Participant not willing to use a suitable method of contraception for 30 days after
receiving study medication treatment;
- Participants with Body Mass Index (BMI - kg/m2) outside the 18 - 36 range at the
Screening Visit;
- Night-shift working or recent travel involving significant change of timezones;
- Excessive caffeine consumption, i.e., consumption higher than 8 cups of standard
caffeinated drinks (tea, instant coffee) or higher than 6 cups of stronger coffee or
other drinks containing methylxanthines such as coca cola or Red Bull per day;
- Participation in a psychological or medical study involving the use of medication
within the last 3 months;
- Previous participation in a study using the same, or similar, emotional processing
tasks;
- Smoker > 10 cigarettes per day or similar levels of tobacco consumption in other
forms.
- Participant received prescribed medication within 28 days prior to First Dose Visit
(apart from their prescribed antidepressant and the contraceptive pill). Participants
who have taken prescription medication may still be entered into the study, if, in the
opinion of the Investigator, the medication received will not interfere with the study
procedures or compromise safety;
- Participant received non-prescription medication, including supplements such as
vitamins and herbal supplements within 48 hours prior to First Dose Visit (apart from
paracetamol). Participants who have taken non-prescription medication may still be
entered into the study, if, in the opinion of the Investigator, the medication
received will not interfere with the study procedures or compromise safety;
- Participant with a known hypersensitivity to PF-04995274 or any other serotonergic
agents;
- Participant with planned medical treatment within the study period that might
interfere with the study procedures;
- Participant who is unlikely to comply with the clinical study protocol or is
unsuitable for any other reason, in the opinion of the Investigator.
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