Brief Treatment Strategies for Major Depressive Disorder: Advice for the Primary Care Clinician

Ivan Valdivia, PhD Candidate; Nadine Rossy, BAC, PhD Candidate


Topics in Advanced Practice Nursing eJournal. 2004;4(1) 

In This Article

Overview of Treatment of MDD

Although there are many potential treatment modalities for MDD, the present article will only address key treatment types that have been empirically supported and are the most relevant to primary care advanced practice nurses. Further, given the realities of modern managed care in the United States, an effort has been made to address brief therapy in the sections that follow.

MDD is a disorder that is often highly manageable; psychotherapy and medications are effective for about 80% of people who seek treatment. Patients generally report experiencing significant benefits 4-6 weeks after treatment initiation.[3]

The following section is meant to provide a brief summary and basic knowledge of the available pharmacotherapies. As such, it is suggested that additional information on any of the mentioned therapies be gathered from external sources such as textbooks of pharmacology and the American Psychiatric Association's Web site.

Multiple drug classes exist for the treatment of MDD. While newer classes of medications are usually the first line of treatment, older medications might be chosen, depending on the subtype of MDD, the age of the patient, cost considerations, and the practitioner's preferences. Most antidepressants have similar rates of efficacy overall and time to onset of effectiveness (eg, they all require 4-6 weeks to achieve maximum therapeutic benefit),[14] but differ in terms of side-effect profiles. Some have demonstrated greater efficacy for select subgroups of depressive disorders, a topic that is beyond the scope of this article.

Tricyclic antidepressants (TCAs). This older, first generation of antidepressants is well researched and has been shown to be effective in hundreds of well-designed randomized controlled trials.[15] Reviews have suggested that 50% to 75% of people treated with this drug class of medication respond favorably,[16] and there is research demonstrating that TCAs might be the class of choice for people suffering from severe MDD[17] and MDD with melancholic features.[18] Examples of this medication group include: amitriptyline (Elavil, Endep), clomipramine (Anafranil), doxepin (Adapin, Sinequan), nortriptyline (Pamelor, Aventyl), and desipramine (Norpramin).

However, there are several caveats associated with TCAs. First, overdose with this drug class is possible; therefore, careful monitoring of use is important for suicidal patients since these medications taken in excess can cause death. Second, the side-effect profile can be difficult to handle for some patients; as a result, 30% to 40% of people using these drugs terminate their use. Common side effects include: blurred vision, dry mouth, constipation, difficulty urinating, drowsiness, weight gain (exceeding 13 lbs. on average), and sexual dysfunction. An advanced practice nurse can help ease the impact of side effects and improve compliance by educating the patient about the management of these side effects.

Monoamine oxidase inhibitors (MAOIs). MAOIs have been shown to be as effective as TCAs,[19] proving especially effective for patients with atypical MDD[20] and for some who have not responded to other classes of medication.[21] Examples of MAOIs include phenelzine (Nardil) and tranylcypromine (Parnate).

Despite their efficacy, at present this drug class is used infrequently due to its potential for severe, often life-threatening interaction with other substances. Most importantly, the patient needs to be thoroughly instructed on the consequences of what has been referred to as the "cheese effect." Since MAOIs are responsible for breaking down tyramine, foods that contain this amine must be avoided or the patient risks a life-threatening hypertensive crisis.

Second, similar to the TCAs, an overdose of MAOIs is possible and can be severe. MAOIs interact negatively with many common over-the-counter medications, necessitating thorough patient education so as to avoid and prevent such interactions. Other common side effects of MAOIs include sedation, weight gain, and orthostatic hypotension. These side effects have often relegated the MAOIs to a second line of defense in treatment planning.

Selective serotonin reuptake inhibitors (SSRIs). Generally the first line of treatment today, this newer class of medications has been shown to be as effective as antidepressants from other classes.[22] The main benefit when compared with the TCAs is that the side-effect profile is often milder. Surprisingly, however, a recent meta-analysis demonstrated that despite these milder side effects, compliance rates appear to be equivalent with other pharmaceutical choices.[23] Some studies have shown that SSRIs are more effective than TCAs for the treatment of atypical MDD[24] and for those who were unsuccessfully treated with TCAs.[25] Examples from this drug class include: fluoxetine (Prozac), citalopram (Celexa), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft).

The main advantage to the SSRIs is that the side effects are often relatively minor and transient. Common side effects include decrease in appetite, nausea, sexual side effects, and headaches. Further, patients are safe from overdose with this class of medication. There is also a cost consideration, since SSRIs are more expensive than TCAs. However, for example, generic fluoxetine is currently a less costly alternative.

Atypical antidepressants. This heterogeneous grouping is not easily summarized because medications under this heading have chemical structures dissimilar to any other category. Since they have been more recently introduced, the research is less conclusive. For example, while it has been shown that reboxetine (Edronax , Vestra) is likely as effective as both the TCAs and the SSRIs,[26] there are data suggesting that trazodone (Desyrel) does not possess the efficacy of other antidepressants.[27,28] Other examples from this group of antidepressants include: nefazodone (Serzone), bupropion (Wellbutrin and Wellbutrin SR), and venlafaxine (Effexor and Effexor XR).

Due to the heterogeneity of this group of medications, the side effects vary. Overall, however, they have fewer, more tolerable, and less toxic side effects than either the TCAs or the MAOIs. Patients who report being unable to manage the side effects of TCAs or the MAOIs may respond better to these drugs.

ECT may be the treatment of choice for patients with severe, unmanageable MDD, if there are catatonic or psychotic symptoms, or for those who need an immediate treatment response such as those who are highly suicidal, pregnant, or have anorexia. Treatment efficacy has been shown to be superior to antidepressant medication.[29] Further, ECT can be helpful for approximately half of those individuals for whom antidepressant medication trials have failed.[30]

This treatment is associated with minimal side effects, which may include posttreatment confusion and anterograde and/or retrograde amnesia, which often resolves in a matter of weeks.[31] Rarely, cognitive side effects are more serious and long lasting, with an uncertain outcome.[32] A usual course of treatment includes 6 to 12 applications every other day, and patients are advised to remain on medications subsequent to positive treatment response.[33] A primary care advanced practice nurse may consult with a psychiatrist in order to assess the suitability of ECT.

Psychological interventions, especially cognitive-behavioral therapy and similar approaches, have consistently shown comparable or superior effects compared with psychotropic medications.[34] In addition, there is evidence that psychological interventions are more cost effective than antidepressant medications.[35] As with any course of treatment, the clinician and patient should discuss the pros and cons of each treatment approach. An important benefit of psychological interventions is that there are no side effects to contend with, save for the required time commitment.

The following section provides a brief overview of 2 of the evidence-based psychological treatment approaches for MDD. Primary care advanced practice nurses who are likely to see patients with MDD should be aware of these approaches, both to facilitate referral to specialists as well as to use some of these techniques within their own practice as they see patients with MDD.

Cognitive-behavioral therapy (CBT). CBT emerged from cognitive theories of depression. Briefly, proponents of the cognitive theory of depression[36] contend that thoughts, feelings, and behaviors are connected; depression is thought to be maintained by (and perhaps even emerge from) distorted and biased cognitions that affect the individual's view of his future, himself, and his environment. Further, such cognitions are thought to be rigid and ubiquitous. They are internal (ie, negative thoughts are directed toward the self), stable (ie, the perceived negative state is believed to be unchangeable), and global (ie, the negativity is pervasive).

While directly changing feelings is difficult to accomplish, it is postulated that changing behaviors and thoughts is less daunting. CBT fosters a collaborative working relationship between the clinician and the patient where a scientific approach is adopted. CBT encourages the application of several mini "experiments," where patients add, remove, and change certain aspects of their thoughts and behaviors to determine the specific effect.

For example, typical depressive cognitions are systematically examined over time and themes are identified. Subsequently, automatic thoughts (ie, thoughts that are fleeting and often evaluative) are isolated and challenged. Core beliefs (ie, an individual's theories about the world in general) undergo a similar dismantling process. All the while, the patient is encouraged to increase participation in certain activities while reducing others (see next section below for more details). Studies have shown that clinicians of varied disciplines can effectively implement CBT if the professional, such as an advanced practice nurse, undergoes thorough training beforehand.[37] The course of treatment generally lasts from 10 to 12 sessions and is termination-oriented, vs long-term oriented.

CBT has been consistently shown to be superior to both placebo and no treatment conditions,[38,39,40,41] and it has been shown that CBT is either as effective or more effective than other types of psychotherapy.[42] CBT's relative efficacy (ie, in comparison with psychotropic medications) is only called into question when dealing with severe depression. However, many studies have failed to demonstrate this limitation to CBT.[43,44]

Interpersonal therapy (IPT). IPT is a brief, highly structured manual-based form of psychotherapy that differs from CBT primarily in its focus. The goal of IPT is to address deficits in one's social sphere, helping the individual to better their communication skills and self-concept by moving toward and fostering interpersonal relationships.[45] While MDD is not necessarily caused by interpersonal events, it can appear in an interpersonal context and is interdependent with the illness. A typical course of IPT will run from 12 to 16 weeks.

IPT did not emerge from one unified theory of human behavior, but was influenced by the work of Bowlby[46,47] in the area of attachment, and Sullivan's[48] theories of Dynamisms and Personifications. Proponents of the treatment have postulated that depression is the combination of symptom formation, decline in social functioning, and personality contributions. Given these assumptions, a clinician using IPT would typically focus on 1 or more of the following areas of concern: (1) complicated grief due to loss, (2) role transitions that place strain on relationships, (3) interpersonal disputes that have a bearing on the health of relationships and the support received, and (4) interpersonal deficits. The clinician would concentrate on these areas of weakness in interpersonal functioning. The techniques used to address the above 4 areas of concern are very similar to methods found in CBT. This is especially apparent when using the therapeutic relationship as a point of examination.

Studies have shown that IPT is as effective as CBT in general,[49,50] although there is some evidence that it is more effective than CBT in cases of severe depression when combined with psychotropic medications.[51] Finally, there is evidence that IPT may be less effective than CBT for depressed patients who also have personality disorders.[49,52] As with CBT, it is necessary to be thoroughly trained in this structured therapy before the concepts[45] can be applied.

A brief note on combining psychotherapy and medications. Evidence suggests that a single mode of treatment should generally be selected. The literature has shown that combinations of psychotropic medications and psychotherapy are not more effective than one treatment modality alone for those patients with mild to moderate MDD. However, there is benefit to combining modalities for those individuals who have either a severe or recurrent form of MDD.[19] It is important to understand that this is an area of consistent controversy. Table 2 provides recommended print and online resources on depression.


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