A big problem with treatment of depression with antidepressants is that it is literally a guessing game, as there are dozens of antidepressants to choose from. There is no scientific process in choosing which antidepressant to start…basically, psychiatrists choose the antidepressant they are most comfortable prescribing. However, this guessing game has bad outcomes, as most patients with depression do not respond to the first antidepressant they are prescribed, and it may take several months or years before the right antidepressant or combination is found to combat depression. Predicting who will respond to the various antidepressant medications would improve outcomes, as more people with depression would respond to quicker and be subjected to less experimentation and guessing.
The guessing game for prescribing antidepressants in depressed people might soon be a thing of the past. A recent study has revealed that different clinical presentations of depression has different neurotransmitter deficiencies, and this may have clinical implications in terms of choice of antidepressant treatment. Homan and colleagues (2015) induced tryptophan depletion and catecholamine depletion in depressed subjects and healthy controls. Tryptophan depletion leads to decreased CNS (Central Nervous System) concentrations of the neurotransmitter serotonin, while catecholamine depletion leads to decreased CNS concentrations of the neurotransmitter norepinephrine (also called noradrenaline). What they found was that tryptophan depletion (serotonin deficiency) produced more depressed mood, sadness, and hopelessness, while catecholamine depletion (norepinephrine deficiency) produced more concentration problems, low energy, psychomotor retardation (inactivity), and somatic anxiety (physical symptoms of anxiety).
So what this study has ingeniously uncovered is that different subtypes of depression can be traced to different neurotransmitter deficiencies. But we need to first discuss the 4 different types of unipolar depression:
- Melancholic depression
This is a rare type of depression, and it is characterized by low energy, poor concentration, and psychomotor disturbance (slowed or agitated movements).
- Non-melancholic depression
This is the most common type of depression, and is characterized by depressed mood, and problems with relationships or work.
- Atypical depression
A less common type of depression, characterized by leaden paralysis, rejection hypersensitivity, hypersomnia, and increased appetite/weight gain.
- Psychotic depression
Another less common type of depression, characterized by depressive symptoms and psychotic symptoms (delusions and hallucinations).
The Homan study outlined 2 different clinical presentations of depression corresponding to tryptophan depletion and catecholamine depletion. These 2 different clinical presentations of depression in the Homan study maps onto 2 of the 4 subtypes of depression. Namely, melancholic depression is associated with norepinephrine deficiency, while non-melancholic depression is associated with serotonin deficiency. Therefore, melancholic depression (with more physical symptoms of depression) will tend to respond to antidepressants which increase norepinephrine in the CNS, such as venlafaxine (Effexor) and duloxetine (Cymbalta), whereas non-melancholic depression (with more psychological symptoms of depression) will tend to respond to antidepressants which increase serotonin, such as sertraline (Zoloft) and fluoxetine (Prozac). More studies are needed to confirm this study, and more studies should focus on which antidepressants are most effective for the different types of depression.