Antidepressant Effects on cAMP Specific Phosphodiesterase (PDE4) in Depressed Patients

You may not qualify if:

• Subjects will be recruited who are drug-na(SqrRoot) ve or who have not received psychotropic drugs for at least 2 weeks (6 weeks for fluoxetine) prior to scanning. Effective medications will not be discontinued for the purposes of the study.
• Subjects will also be excluded if they have:
• serious suicidal ideation or behavior
• psychosis
• medical conditions or concomitant medications that are likely to influence PET measurement or have significant interactions with sertraline, citalopram or escitalopram.
• a history of drug or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM-IV criteria)
• positive urine drug screen
• current pregnancy (as documented by pregnancy testing prior to scanning)
• major depression that arose following another major medical or psychiatric condition, and
• prior participation in other research protocols within a year such that radiation exposure would exceed the annual guidelines
• For patients who have two \[C-11\]rolipram PET scans, one before and another after SSRI treatment, previous failures of or intolerance to SSRI may not allow for treatment in the current protocol. In clinical practice, medication can be switched between sertraline and citalopram/escitalopram because sertraline and citalopram/escitalopram have somewhat different therapeutic effects and adverse reactions. Along these lines, we will consider citalopram and its enantiomer escitalopram as being equivalent to each other. Patients will therefore be excluded from the study with two \[C-11\]rolipram PET scans if they previously failed to respond to adequate treatment trials of all medications available for use in the study, or if they have a history of being unable to tolerate all of the study medications. Specifically, patients will be excluded from the study with two \[C-11\]rolipram PET scans if they:
• j) previously proved unresponsive to therapeutic trials of both sertraline and citalopram/escitalopram.
• k) previously developed allergic reactions to both sertraline and citalopram/escitalopram, or discontinued both sertraline and citalopram/escitalopram due to an adverse effect
• l) through any combination of therapeutic unresponsiveness and adverse medication effects, are unsuitable for treatment with both sertraline and citalopram/escitalopram
• m) prolonged QTc in ECG
• +3 more criteria