Treatment regimens for managing depression in family practice

Journal of Family Practice, Dec, 2003 by Adam Keller Ashton, Dale A. D'Mello, Bezalel Dantz, Jaye Hefner, F. George Leon, Gary A. Matson, C. Brendan Montano, James F. Pradko, Norman Sussman, Bertrand Winsberg

This article presents suggestions, strategies, and practices--based largely on the authors" clinical experience--to help clincians manage treatment for depression into remission, monitor the remission, and prevent relapse. Issues of comorbidities must also be considered.

* FIRST-LINE THERAPY: STRATEGIES FOR SELECTING AN ANTIDEPRESSANT

Based on clinical experience, the authors believe that clinicians should evaluate the effects of currently used antidepressants in terms of the actions of serotonin, norepinephrine, and dopamine and their potential effect on individual patients. It should, however, be noted that no clinical trials have addressed this issue. Consideration of neurotransmitter actions may not relate at all to efficacy of agents. However, modulation of levels of these chemicals produces effects that may be beneficial, detrimental, or neutral in terms of side effects--and affect the success of treatment in terms of both treatment-related side effects and patient compliance. Thus, clinicians may be able to more effectively tailor treatment to provide the most benefit to the patient.

An approach to treatment based on neurotransmitter effects

The clinical decision tree in Figure 1 may be useful in delineating how and why certain treatment decisions may match potential side effects to patients' needs. This chart likely represents a departure from current practice methodologies in that it directs one toward specific antidepressant medications based on comorbid illness and anticipated side effects, as opposed to the more common symptomatic approach that targets specific manifestations of a patient's depression.

[FIGURE 1 OMITTED]

The algorithm identifies specific questions (and their order) that the authors believe should be asked by family physicians when selecting antidepressant medication for a newly diagnosed patient with depression.

This algorithm is not meant to imply cause and effect; rather, it proposes a strategy for initiating antidepressant therapy based on the likelihood that this medication should be helpful for, and well tolerated by, patients with specific presentations and comorbidities, and those for whom side effects may make an agent more beneficial, neutral, or contraindicated. With practice, the authors believe, this approach may make the treatment of depression more scientific and less taxing for the clinician.

Evaluating levels of neurotransmitters

The first question considered by a clinician is "Is it likely that elevating dopamine levels will benefit the patient?" The authors feel this question must be asked first because dopamine is the only neurotransmitter whose levels can be increased, decreased, or left unchanged by specific antidepressants (see Summary of neurotransmitter action and its potential desirable and desirable effects, Table 2, page 37).

* The SSRIs, which do not block the serotonin receptor 5H[T.sub.2a], are associated with a suppression of dopamine

* Serotonergic antidepressants that do block the receptor 5H[T.sub.2a] (eg, nefazodone and mirtazapine) are generally neutral with regard to dopamine levels

* Bupropion, an antidepressant with very distinct dopaminergic activity, has been shown to increase dopamine by blocking its reuptake.

For these reasons, the authors believe it makes good clinical sense to consider dopamine first.

The next step in the therapeutic decision-making process assesses the potential benefits of serotonin, followed by norepinephrine. In this way, the authors believe that simple application of the known clinical correlates of neurotransmission can be used as a very powerful tool in the selection of an initial antidepressant--a synthesis of science and clinical expertise.

Potential benefits of specific neurotransmitter activity on patient symptoms

By first evaluating dopamine, the authors think it may be possible to alleviate common patient complaints of apathy, tiredness, and lack of motivation--all of which may be improved by increasing dopamine levels. The authors have observed that when these complaints persist in patients treated with a nondopaminergic antidepressant, reevaluation often reveals the depression itself to be in remission, although apathy and tiredness remain. The authors believe that this patient may benefit from the use of a dopaminergic antidepressant, either alone or as part of combination therapy.

Additionally, it has been noted that patients who experience cravings, (1-3) attention deficit hyperactivity disorder (ADHD),(4,5) hyposexual desire disorder (low libido), (6) and low motivation (7,8) may benefit by elevation of dopamine levels.

Patient characteristics: potential benefits of neurotransmitter modulants

The clinician can also assess the potential impact of an agent. For instance, a patient whose personality suggests that he/she is easy to anger may benefit from reduced dopamine levels. (9)

Increasing serotonin levels may be helpful in patients who experience premature ejaculation[TM] or who seem prone to worry or panic. However, in situations involving marital discord, this agent may be counterproductive, potentially increasing the risk of reduced libido or patient apathy. (11,12)