Textbook of Psychiatry/Psychopharmacology

alcoholism treatment

From Wikibooks, open books for an open world

The use of psychotropic medicines to treat psychiatric illness has increased dramatically in recent times. Although the biological etiologies of most psychiatric disorders are still unclear, effective pharmacological treatments have been developed over the past 50 years that have become part of the standard of care in the treatment of most major psychiatric disorders.

Psychiatric medications are part of the armamentarium of most practicing physicians, regardless of medical specialty. In the United States, although most severe types of mental illness are likely to be treated by psychiatrists, most prescriptions for psychotropics (e.g. anxiolytics and newer antidepressants) are written by non-psychiatrists.(Stagnitti, 2008) Psychiatric medications are consistently prominent in the list of the top 200 most commonly prescribed medications, and in the top 20 pharmaceuticals in terms of sales in the United States. From 2003-2007 antidepressants, as a class, topped all other therapeutic classes for the overall number of dispensed prescriptions in the U.S.(IMS Health, 2007)

As in the treatment of all medical disorders, a thorough evaluation must precede psychiatric diagnosis and subsequent psychopharmacological treatment. A complete history should be obtained and the patient should be examined. Medical or neurological etiologies that may contribute to the presentation of psychiatric illness should be identified and addressed. Nearly 10% of patients presenting with a psychiatric complaint will turn out to have a medical problem as the primary cause.(Hall, Popkin et al. 1978) Active substance abuse, if present, should be treated before or at the same time that pharmacological therapies are initiated.

The clinician should then decide if the condition requires medication treatment. Mild to moderate anxiety and depression generally respond equally well to supportive interventions or psychotherapy.(APA, 2004; Barkham and Hardy, 2001; Cuijpers, van Straten et al. 2009; King, Sibbald et al. 2000) On the other hand, if the psychiatric disorder or symptoms are severe, or if psychosis, mania, or dangerousness are present, then psychopharmacological treatments (and referral to a psychiatrist) are indicated. Although many primary care physicians may be quite comfortable with their ability to manage psychiatric illness, the amount of monitoring that is required to provide adequate follow-up should be taken into account before initiating treatment. When treating moderate to severe psychiatric illness, optimum therapy includes the use of concomitant psychotherapy in addition to pharmacotherapeutic measures.(APA, 2004; APA, 1998; APA, 2000; Keller, McCullough et al. 2000; Banerjee, Shamash et al. 1996; Reynolds, Frank et al. 1999; Katon, Von Korff et al. 1999; Miklowitz, 2008)

Placebo-controlled randomized clinical trials, using strict exclusionary criteria when selecting subjects, have traditionally been used to study a psychiatric medication’s efficacy (i.e. the ability of the medication to treat the condition better than placebo under controlled conditions). For example, studies comparing an antidepressant to placebo may use an 8 week double-blind parallel design and include subjects with major depression but without any other medical or psychiatric co-morbidities. Response may be defined as a 50% improvement in a chosen outcome rating scale. These efficacy studies also provide the response data that pharmaceutical companies must submit to the Food and Drug Administration (FDA) to obtain indications for developed drugs.

Effectiveness studies, on the other hand, are often larger, naturalistic studies that attempt to approximate "real world" conditions by studying patients who may have psychiatric and medical co-morbidities, and by relying on broader outcome measures for assessing response. These studies may compare outcomes of treatment with multiple medications. As such, effectiveness studies complement our understanding of drug efficacy.(Summerfelt and Meltzer, 1998) Recent National Institute of Mental Health (NIMH) sponsored effectiveness studies have the added benefit of funding from a neutral (non-pharmaceutical industry) source, thereby avoiding possible study design shortcomings or evaluator biases that may influence study results.(Heres, Davis et al. 2006; Osser, 2008) These studies include (1) the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE),(Keefe, Bilder et al. 2007; Lieberman, Stroup et al. 2005) (2) the Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D),(Rush, Trivedi et al. 2006; McGrath, Stewart et al. 2006; Nierenberg, Fava et al. 2006; Trivedi, Fava et al. 2006; Fava, Rush et al. 2006) (3) the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD),(Sachs, Nierenberg et al. 2007; Goldberg, Perlis et al. 2007; Miklowitz, Otto et al. 2007) (4) the Clinical Antipsychotic Trials of Intervention Effectiveness—Alzheimer’s Disease (CATIE-AD),(Schneider, Tariot et al. 2006; Sultzer, Davis et al. 2008) and (5) the National Institute of Alcohol Abuse and Alcoholism (NIAAA) sponsored Combined Pharmacotherapies and Behavioral Interventions Study (COMBINE).(Anton, O'Malley et al. 2006; Anton, Oroszi et al. 2008) Findings from these studies are now influencing clinical psychiatric practice.

In clinical practice, even after an appropriate diagnosis is made for an individual patient and the decision is made to use a medication from a particular pharmacotherapeutic class (e.g. an antidepressant for depression), multiple variables need to be considered prior to selecting a specific agent. The physician should take the following into account: (1) patient acuity and the need to address the most dangerous presenting symptoms (e.g. behavioral agitation, suicidality, catatonia, etc.) first, (2) the patient’s past treatment history, (3) pre-existing medical conditions in order to minimize any increase in medical risk, (4) possible medication interactions, (5) the time required for amelioration of symptoms, (6) a medication’s known side effect profile and how this may affect presenting symptoms, (7) the need to minimize the use of polytherapy, (8) possible pharmacogenetic factors and hereditary patterns of drug response and tolerance, and (9) financial cost-benefit considerations. The practicing physician should consider these issues prior to initiating treatment.(Ansari, Osser et al. 2009)

Characteristics of the major classes of psychotropics and their use in adults are discussed below. Children and adolescents may tolerate or respond to these medications differently. The use of psychopharmacological therapies in these age groups is outside the scope of this chapter.


Antidepressants [ edit ]

Currently available antidepressants primarily affect the norepinephrine and serotonin (monoamine) neurotransmitter systems.(Nestler, Hyman et al. 2009) Norepinephrine systems originate primarily from the locus ceruleus (and lateral tegmental areas) and project widely to almost all areas of the brain and spinal cord. Serotonergic neurons reside in the raphe nuclei in the brainstem and diffusely make contact with all areas of the brain. Most antidepressants increase the available amount of norepinephrine and/or serotonin at the neuronal synapse by decreasing the reuptake of these neurotransmitters into the pre-synaptic cell. They do this by inhibiting the norepinephrine transporter and/or the serotonin transporter, or by decreasing the metabolism of these neurotransmitters. Other antidepressants have direct effects on monoamine receptors. Genetic polymorphisms of the norepinephrine and serotonin reuptake transporters (Kim, Lim et al. 2006) as well as polymorphisms of post-synaptic serotonin receptors(McMahon, Buervenich et al. 2006) have been associated with differences in responses to different antidepressants. Once synaptic changes have taken place with treatment, long-term adaptations in post-synaptic neurons and resultant changes in gene expression may then be responsible for alleviating depression.(Nestler, Hyman et al. 2009).

Tricyclic Antidepressants (TCAs) [ edit ]

Beginning with the introduction of imipramine in the late 1950’s,(Kuhn, 1958) tricyclic antidepressants were among the first classes of antidepressants developed. They share a tricyclic structure (two benzene rings on either side of a seven-member ring), exhibit variable degrees of norepinephrine and serotonin reuptake inhibition, and are antagonists at several other neurotransmitter receptors.(Hyman, Arana et al. 1995) Examples of commonly used TCAs include the tertiary amines imipramine, amitriptyline, clomipramine, and doxepin, and the secondary amines desipramine (metabolite of imipramine) and nortriptyline (metabolite of amitriptyline). All TCAs can cause the following adverse effects: (1) slowing of intra-cardiac conduction as measured by QRS and QTc prolongation, (2) anticholinergic effects such as dry mouth, urinary retention, and constipation due to muscarinic acetylcholine receptor antagonism, (3) orthostatic hypotension due to peripheral alpha-1-adrenergic antagonism, and (4) sedation and possible weight gain due to histamine (H1) receptor antagonism. For these reasons TCAs need to be started at low doses and increased gradually, giving the patient time to accommodate to these effects. Individual differences in both severity of side effects and therapeutic effects (along with differences in therapeutic serum levels)(Perry, Zeilmann et al. 1994) do exist among individual TCAs. There is some evidence to suggest that TCAs may have a particularly important role in the treatment of severe and psychotic depression.(Hamoda and Osser, 2008)

The cardiac effects of TCAs have contributed to a reduction in their use over the past 20 years. Prolonged QT interval (measured as QTc when corrected for heart rate) may be associated with torsades de pointes, a potentially fatal ventricular arrhythmia (also see section on antipsychotics). All patients should have an ECG to rule out any existing conduction abnormalities prior to considering TCAs. Patients with recent myocardial infarctions should not initiate treatment with these antidepressants. Most importantly, depressed patients who are at risk for suicide and overdose may not be appropriate for treatment with TCAs. It should be noted that a 1-2 week supply of these medications can be fatal in overdose due to the risk of cardiac arrhythmias. Therefore, depending on the patient’s risk of suicide, clinicians may need to limit the number of tablets prescribed with each refill. This concern is significantly lessened with the use of newer antidepressants that are safer in overdose.

TCAs are often used for their mild to moderate analgesic effects in the treatment of chronic pain syndromes.(Magni, 1991) These effects are independent of any effect on mood, with efficacy starting at lower doses, and with response seen earlier than when antidepressants are used for depression.(Magni, 1991; Max, Culnane et al. 1987; Onghena and Van Houdenhove, 1992) The TCAs seem more effective for chronic pain than the selective serotonin reuptake inhibitor antidepressants (SSRIs, see below).(Ansari, 2000; Fishbain, 2000; Saarto and Wiffen, 2007)

Monoamine Oxidase Inhibitors (MAOIs) [ edit ]

Monoamine oxidase is an enzyme that acts to metabolize monoamines, both intracellularly and extracellularly. Its inhibition increases the amount of serotonin, norepinephrine and dopamine available for neurotransmission. The first MAOI, iproniazide, an anti-tuberculosis drug, was discovered in the 1950’s. Tranylcypromine, phenelzine, isocarboxazid, and more recently transdermal selegiline are MAOIs currently available in the United States for the treatment of depression. These antidepressants may be particularly effective for patients with atypical depression (i.e. depression characterized by hyperphagia and hypersomnia).(Quitkin, Stewart et al. 1993)

Although serotonergic side effects—see SSRIs below—as well as orthostatic hypotension can occur with MAOIs, there are two other primary areas of concern that limit the use of these agents.(Lippman and Nash, 1990) First, dangerous interactions can occur with certain foods, such as aged cheeses and wines that contain biogenic amines such as tyramine. MAOIs can inhibit the metabolism of tyramine in the intestine, increasing its general circulation and ultimately leading to an increase in sympathetic outflow and an adrenergic ("hypertensive") crisis characterized by severe hypertension, headache, and increased risk of stroke and cerebral hemorrhage. Patients need to be advised regarding dietary restrictions before treatment. Also, to prevent hypertensive crisis, MAOIs cannot be combined with medications that have sympathomimetic properties such as some over the counter cold preparations, amphetamines, and epinephrine (which is often added to local anesthetics as a vasoconstrictor).

Secondly, MAOIs if used concomitantly with serotonergic agents, such as SSRIs, may lead to "serotonin syndrome," a potentially fatal condition that is characterized by hyperreflexia, hyperthermia, and tachycardia, and may lead to delirium, seizures, coma and death.(Sternbach, 1991) A two week washout period is required when switching from SSRIs (or any other agents with serotonergic effects) to MAOIs, or vice versa. An exception is when the long half-life SSRI fluoxetine is being discontinued: a five week washout period is needed before starting an MAOI.(Boyer and Shannon, 2005) The treating physician should access appropriate online databases such as the drug-specific DRUG-REAX® System (www.micromedex.com/products/drugreax) or GeneMedRx (www.genemedrx.com) to rule out dangerous drug-drug interactions when considering the use of an MAOI.

Selective Serotonin Reuptake Inhibitors (SSRIs) [ edit ]

SSRIs are antidepressants with a more favorable side effect profile than TCAs and MAOIs and as such are used as first-line antidepressants. As their name implies, SSRIs inhibit the serotonin transporter from reuptaking serotonin at the neuronal synapse. Interestingly, polymorphisms at the promoter region of the serotonin transporter gene (SLC6A4) may influence response to SSRIs: the presence of the "short" form of the serotonin transporter gene may be associated with poor response to SSRIs, whereas the presence of the "long" allele may be associated with positive drug response (Malhotra, Murphy et al. 2004) and better tolerability.(Murphy, Hollander et al. 2004) Recent data from the large NIMH STAR*D study, however, have failed to support the association between this polymorphism and drug response.(Kraft, Peters et al. 2007; Lekman, Paddock et al. 2008)

Currently available SSRIs include fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and its S-enantiomer escitalopram. Possible mild early side effects (that can be minimized by starting the SSRI at a low dose and increasing the dose gradually) include gastro-intestinal upset, sweating, headaches, jitteriness or sedation. Continuation of these agents may be associated with reversible sexual side effects (i.e. delayed ejaculation, decreased libido, or erectile dysfunction) in 2-73% of treated patients (depending on how questions regarding sexual side effects are asked).(Montejo, Llorca et al. 2001)

SSRIs differ in their propensities to inhibit hepatic cytochrome P450 enzymes (e.g. CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4).(Ereshefsky,

Jhee et al. 2005) Inhibition of hepatic enzymes may lead to decreased metabolism of substrate medications such as warfarin, metoprolol, tricyclic antidepressants, and antipsychotics. This may increase serum levels of these drugs and lead to increased risk of dangerous adverse effects such as bleeding, hypotension, cardiac arrhythmias, and parkinsonian effects, respectively. Among the SSRIs, citalopram and escitalopram are the least likely to inhibit the metabolism of other drugs and are therefore preferred in patients concomitantly treated with multiple other medications. Escitalopram is a more recently marketed, and still expensive, successor to generic citalopram, though it has no clinically significant efficacy advantage.

The relatively benign side effect profiles of SSRIs and their ease of use have contributed to widespread use by clinicians who might not have been comfortable with using earlier antidepressants such as TCAs and MAOIs. In cases of atypical presentations of depression, or depression in the context of recent substance abuse, SSRIs are more readily used even before there is absolute clarity in diagnosis. Under these circumstances, many clinicians believe that the benefits of treatment may outweigh the risks. In the case of depressed patients with concomitant substance abuse, the possibility that some patients may not be able to maintain sobriety because of an underlying major depressive disorder has served as a rationale for beginning antidepressant therapy even when the patient is still actively using.

Although this empirical "trial" of an SSRI (as an antidepressant with a relatively benign side effect profile), in situations where there is less than optimum diagnostic clarity, may be appropriate for some patients, the physician should be aware of at least two major areas of risk. First, all antidepressants can induce mania in the short-term, and overall mood instability in the long-term, in patients with a vulnerability to bipolar disorder. A clear family history should be obtained to investigate whether there is a genetic predisposition to bipolar disorder. Also, clinicians should be aware that younger depressed patients, who may go on later to exhibit manic symptoms, may be incorrectly diagnosed with unipolar depression when in fact they may have a bipolar diathesis. A pre-bipolar presentation of depression (O'Donovan, Garnham et al. 2008) should be suspected in patients with (1) a family history of bipolar depression, (2) a younger age of onset, (3) a family history of completed suicide, (4) past poor response to antidepressants, (5) a history of treatment-emergent agitation, irritability, or suicidality, and (6) a history of post-partum psychosis.(Chaudron and Pies 2003) Depressed patients with these characteristics may have bipolar rather than unipolar depression and therefore should not be reflexively started on an antidepressant.(Ghaemi, Ko et al. 2002; O'Donovan, Garnham et al. 2008; Phelps, 2008)

Secondly, antidepressants have been associated with an increased risk of treatment-emergent suicidality—this occurs in about 4% of treated patients versus 2% on placebo—especially in children, adolescents and young adults as noted in the current package inserts of all antidepressants. It is still unclear if this risk is significant in adults over age 25. The reasons for this increase in suicidality are not clear, although increased agitation (e.g. akathisia) or activation as a side effect,(Harada, Sakamoto et al. 2008) or the possible emergence of "mixed" manic symptoms (mania combined with dysphoric mood) in depressed bipolar patients as noted above, may be responsible. Despite the concern that antidepressants may infrequently increase suicide risk, it should be noted that overall rates of suicide in the United States had actually decreased over a prior 15 year span probably due to the increasingly widespread use of SSRI antidepressants.(Grunebaum, Ellis et al. 2004) Nevertheless, the concern about treatment-emergent suicidality argues for the need for careful evaluation and diagnosis, increased discussion of risks and benefits of treatment with patients (and family when appropriate), and close monitoring of all patients beginning antidepressant therapy. Prescribing antidepressants when indicated, coupled with these steps, is more appropriate than withholding antidepressants in unipolar depressed patients who are more likely to benefit rather than come to harm from these treatments.(Bridge, Iyengar et al. 2007) Unfortunately, recent surveys have found that instead of the increase that was hoped for in the monitoring of patients undergoing antidepressant therapy,(Morrato, Libby et al. 2008) there has been an overall decrease in the use of antidepressants and a recent increase in the overall rates of suicide(Gibbons, Brown et al. 2007) since the "black box" warnings about treatment-emergent suicidality were issued.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) [ edit ]

The SNRIs, venlafaxine, desvenlafaxine and duloxetine, are dual action serotonergic and noradrenergic antidepressants that would be expected to have efficacy similar to TCAs though without anticholinergic, antihistaminic, hypotensive, or cardiac side effects. Venlafaxine is primarily serotonergic at lower doses and has a dual action only at higher doses.(Feighner 1999; Richelson 2003) Using venlafaxine at lower doses (i.e. less than 150 mg per day), therefore, should not be presumed to be any different from using an SSRI. At higher doses it can have a mild to moderate hypertensive effect,(Johnson, Whyte et al. 2006; Mbaya, Alam et al. 2007) although patients with effectively treated hypertension can tolerate venlafaxine without an increase in blood pressure(Feighner, 1995). Duloxetine, which exerts a dual action effect throughout its dose range (i.e. not only at higher doses as with venlafaxine),(Stahl and Grady, 2003) can also increase blood pressure, although the effect may be less pronounced and clinically insignificant.(Raskin, Goldstein et al. 2003; Wohlreich, Mallinckrodt et al. 2007) SNRIs, like TCAs, are more likely to induce mania in bipolar patients than SSRIs.(Leverich, Altshuler et al. 2006)

Because low-dose TCAs have been shown to be modestly effective in the treatment of chronic pain syndromes, and SNRIs have a similar dual action, they have been proposed for the treatment of chronic pain symptoms as well. Duloxetine is currently the only antidepressant with an FDA indication for diabetic neuropathy and fibromyalgia. Although the more benign side effect profile of duloxetine may make it the preferred agent in a patient for whom the risks associated with a TCA are unacceptable, there is no evidence to suggest it would be more efficacious for the treatment of pain than the more cost-effective TCAs.

Antidepressants with Other Mechanisms [ edit ]

Bupropion is an antidepressant with a poorly understood mechanism of action. It is believed to exert its effect through dopamine reuptake inhibition although it is unclear why this mechanism alone should provide it with an antidepressant effect. Some data suggest that it may also exhibit norepinephrine reuptake inhibition.(Richelson, 2003; Rosenbaum, Arana et al. 2005) Bupropion has a different side effect profile than antidepressants that significantly affect the serotonergic systems. It is unlikely to cause sexual side effects or weight gain—two of the most common reasons for medication non-adherence in patients. However, bupropion can lower seizure threshold and is therefore contraindicated in patients who are seizure-prone (e.g. patients with a history of seizures or conditions that increase seizure risk, such as eating disorders, or active withdrawal from alcohol or benzodiazepines). The risk of seizure is dose dependent: this should be kept in mind when combining bupropion with CYP2D6 inhibitors such as paroxetine or fluoxetine that may increase bupropion serum levels. Among antidepressants, bupropion is least likely to cause mania in bipolar patients.(Leverich, Altshuler et al. 2006; Post, Altshuler et al. 2006)

Mirtazapine increases both serotonin and norepinephrine at the neuronal synapse (and therefore like SNRIs has "dual actions") through mechanisms distinct from reuptake inhibition. It is an antagonist at alpha-2-adrenergic autoreceptors thereby increasing norepinephrine and serotonin release, and it blocks post-synaptic 5HT-2A, 5HT-2C, and 5HT-3 serotonin receptors.(Feighner, 1999) (Mianserin, an earlier analog of mirtazapine marketed in Europe, has a similar mechanism of action). Mirtazapine can improve appetite (likely through 5HT-3 and H1 antagonism) and sleep (through H1 antagonism). As expected, these immediate effects can be very beneficial in the treatment of the acutely depressed patient with poor oral intake and insomnia. Weight gain however can be a concern over the long run.

Nefazodone is a post-synaptic 5HT2 antagonist with weak serotonin and norepinephrine reuptake inhibition.(DeVane, Grothe et al. 2002) Although nefazodone can improve sleep, and is neutral in regard to weight gain and less likely than SSRIs to cause sexual side effects, it is used much less often since it was found to produce rare (1 in 250,000 to 300,000 patient-years), but severe, hepatotoxicity.(Gelenberg, 2002) Trazodone, a structurally similar antidepressant, is used primarily as a hypnotic (it proved to be too sedating for most patients at doses necessary for antidepressant effect). Trazodone can commonly cause orthostasis and should be used cautiously in the elderly. Priapism is a rare side effect that should be discussed with male patients before treatment.

Further Notes on the Clinical Use of Antidepressants [ edit ]

Clinical practice today emphasizes the use of newer ("second generation") antidepressants including bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone and venlafaxine. As discussed above, the older tricyclics and MAOIs are not first-line because of their greater toxicity and risk of harm from overdose. In a meta-analysis of 203 studies comparing the efficacy and side effects of these newer antidepressants, no substantial differences in effectiveness were found.(Gartlehner, Gaynes et al. 2008) The authors recommended that antidepressants be selected on the basis of differences in expected side effects and cost (i.e. – use generic products over brand items). Another review of 117 trials concluded that sertraline had the most favorable balance among benefits, side effects, and acquisition cost.(Cipriani, Furukawa et al. 2009)

The STAR*D study (Sequenced Treatment Alternatives to Relieve Depression), sponsored by the NIMH was a study of medications for the treatment of major depression. It produced important insights into the optimum use of pharmacotherapy for this disorder. STAR*D started with almost 4,000 heterogeneous "real world" depressed patients, who were treated by "real world" clinicians such as primary care doctors. Patients agreed to have up to 4 medication trials with the goal of achieving remission from their depression. Each trial lasted up to 14 weeks. Patients started with citalopram for the first trial. If response was unsatisfactory, they could have a switch to one of three antidepressants, or an augmentation with one of two augmenting agents. For the third trial, there were other switches or augmentations available, and finally for those still depressed and still willing to undergo the fourth trial, there was the choice of an MAOI or a combination of venlafaxine and mirtazapine. The latter has been referred to informally as "rocket fuel" because of the four different neurotransmitter alterations that this combination is thought to induce.(McGrath, Stewart et al. 2006) Key findings from STAR*D include the following:

  • Citalopram did not work well if patients met the DSM-IV criteria for melancholic features.(McGrath, Khan et al. 2008)
  • The switches in the second trial (to another SSRI: sertraline, to bupropion, or to venlafaxine) had equal efficacy.
  • The augmentations in the second trial (buspirone--discussed in anxiolytic section below--or bupropion) worked equally well.
  • Nothing worked well in trials one or two if patients had significant anxiety symptoms along with their depression.(Fava, Rush et al. 2008) However, a recent study with adjunctive aripiprazole (an antipsychotic discussed below) added to an SSRI found good results in patients with depression mixed with anxiety, in a post-hoc analysis.(Trivedi, Thase et al. 2008) This needs replication in a prospectively designed study.
  • In the third trial, switching to a tricyclic antidepressant worked fairly well. It might have worked better if clinicians had dosed it properly and used plasma levels to monitor adequacy of dosage.
  • Adding lithium (discussed in the mood stabilizer section below) did not work as well as adding triiodothyronine in the third trial, but lithium might have done better if clinicians had dosed it properly.
  • In trial 4, the MAOI did not do well compared to the venlafaxine/mirtazapine combination, but clinicians underdosed the MAOI. Unfortunately, for the few patients who improved from either treatment, early relapse was common.

As a group, STAR*D subjects were not particularly interested in psychotherapeutic treatment for their depression. Psychotherapy was available as an option in the second treatment trial, but patients could elect to drop it from the option list and most did so.(Wisniewski, Fava et al. 2007) The modest remission rates seen in STAR*D may reflect that a major component of the improvement in depression seen in research and clinical settings comes from the non-specific, interpersonal supportive aspects of care including the therapeutic alliance. STAR*D patients might have been less susceptible to these benefits than other patients who are more invested in psychosocial treatments of their disorder. It is hoped that future studies will improve our ability to select the best treatments for each patient, psychopharmacological and psychotherapeutic, depending on their needs and preferences.

Table 1 summarizes characteristics of commonly used antidepressants.(WHO, 2007; PDR, 2008; Hyman, Arana et al. 1995; Perry, Zeilmann et al. 1994; Rosenbaum, Arana et al. 2005; Stahl 2005; Taylor, Paton et al. 2007)


Similar articles: