Fluoxetine also has antagonist properties at 5HT2C receptors, which could increase norepinephrine and dopamine neurotransmission
How Long Until It Works
Some patients may experience increased energy or activation early after initiation of treatment
Onset of therapeutic actions usually not immediate, but often delayed 2-4 weeks
If it is not working within 6-8 weeks, it may require a dosage increase or it may not work at all
May continue to work for many years to prevent relapse of symptoms
If It Works
The goal of treatment is complete remission of current symptoms as well as prevention of future relapses
Treatment most often reduces or even eliminates symptoms, but not a cure since symptoms can recur after medicine stopped
Continue treatment until all symptoms are gone (remission) or significantly reduced (e.g., OCD, PTSD)
Once symptoms are gone, continue treating for 1 year for the first episode of depression
For second and subsequent episodes of depression, treatment may need to be indefinite
For anxiety disorders and bulimia, treatment may also need to be indefinite
If It Doesn’t Work
Many patients have only a partial response where some symptoms are improved but others persist (especially insomnia, fatigue, and problems concentrating in depression)
Other patients may be nonresponders, sometimes called treatment-resistant or treatment-refractory
Some patients who have an initial response may relapse even though they continue treatment, sometimes called “poop-out”
Consider increasing dose, switching to another agent or adding an appropriate augmenting agent
Consider psychotherapy
Consider evaluation for another diagnosis or for a comorbid condition (e.g., medical illness, substance abuse, etc.)
Some patients may experience apparent lack of consistent efficacy due to activation of latent or underlying bipolar disorder, and require antidepressant discontinuation and a switch to a mood stabilizer
Best Augmenting Combos for Partial Response or Treatment Resistance
Trazodone, especially for insomnia
Bupropion, mirtazapine, reboxetine, or atomoxetine (add with caution and at lower doses since fluoxetine could theoretically raise atomoxetine levels); use combinations of antidepressants with caution as this may activate bipolar disorder and suicidal ideation
Modafinil, especially for fatigue, sleepiness, and lack of concentration
Mood stabilizers or atypical antipsychotics for bipolar depression, psychotic depression, treatment-resistant depression, or treatment-resistant anxiety disorders
Fluoxetine has been specifically studied in combination with olanzapine (olanzapine-fluoxetine combination) with excellent results for bipolar depression, treatment-resistant unipolar depression, and psychotic depression
Benzodiazepines
If all else fails for anxiety disorders, consider gabapentin or tiagabine
Hypnotics for insomnia
Classically, lithium, buspirone, or thyroid hormone