Medication Summary
Antidepressants are effective in treating dysthymia; the mean response for any antidepressant in a review study was 55% among dysthymic patients (compared with 31% response for placebo). Doses are the same as those used for major depression. A systematic review of antidepressant treatment in dysthymia suggested that SSRIs, tricyclic antidepressants, and monoamine oxidase inhibitors (MAOIs) are all equally effective, but SSRIs may be slightly better tolerated. Success has also been reported with more noradrenergic agents such as mirtazapine (Remeron), nefazodone (Serzone), venlafaxine (Effexor), duloxetine (Cymbalta), and bupropion (Wellbutrin).
Comparisons of agents within or between classes have not been reported for dysthymia. A 2007 research summary by the Agency for Healthcare Research and Quality (AHRQ) identified no head-to-head trial comparing different second-generation antidepressants for treatment of dysthymia; comparison between placebo-controlled trials was stymied by significant differences in population characteristics.
The AHRQ noted that in a fair-quality placebo-controlled study, a subgroup of patients older than 60 years showed a significantly greater improvement on paroxetine than did those on placebo, whereas paroxetine was no more effective than placebo in a subgroup of patients younger than 60 years. [32]
While the older antidepressants, such as tricyclics and MAOIs, are effective, the SSRIs are the medications most commonly used for dysthymia, likely because of their relative safety and milder side-effect profile. Given that dysthymia is a chronic condition, tolerability is important to facilitate compliance over the long-term.
Little data exist for choosing one antidepressant over another unless (1) the risk of a particular adverse effect is to be avoided, (2) the patient has a history of prior response to a particular drug, or (3) a drug is known to have been effective for a member of the patient's family.
Of note, antidepressants may cause a temporary worsening of anxiety symptoms; lower doses, slower titration, or temporary use of benzodiazepines (if not contraindicated, for example, because of a substance use disorder) may mitigate anxiety and improve tolerability.
Pediatric safety concerns
Physicians should be aware of the US Food and Drug Administration (FDA) black box warning regarding antidepressant treatment in children and younger adults and use appropriate caution when considering the risks and benefits of antidepressant treatment in these populations.
In December 2003, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) issued an advisory that most SSRIs are not suitable for use by persons younger than 18 years for treatment of "depressive illness." After review, this agency decided that the risks to pediatric patients outweigh the benefits of treatment with SSRIs, except fluoxetine (Prozac), which appears to have a positive risk-benefit ratio in the treatment of depressive illness in patients younger than 18 years.
In October 2003, the FDA issued a public health advisory regarding reports of suicidality in pediatric patients being treated with antidepressant medications for major depressive disorder. This advisory reported suicidality (ideation and attempts) in clinical trials of various antidepressant drugs in pediatric patients. The FDA has asked that additional studies be performed because suicidality was noted in treated and untreated patients with major depression and thus could not be definitively linked to drug treatment.
Augmentation
Treatment resistance is common in depression and dysthymia. Patients should be closely tracked for residual symptoms and, if symptoms have not remitted, a medication change or an augmentation should be considered to target full remission. [15] Data guiding antidepressant augmentation are drawn from studies in treatment-resistant major depression. The strongest data exists for lithium and thyroid hormone augmentation.
While thyroid dysfunction is common among people with depression and must be treated, thyroid hormone supplementation is an effective augmentation strategy even for patients with normal thyroid function. [33, 34] Buspirone, bupropion, stimulants, and mirtazapine are commonly used in clinical practice.
Bright-light therapy may be considered as an adjunct treatment, especially for patients who experience an exacerbation of symptoms during the winter. This therapy has been best studied in patients with seasonal affective disorder, but limited evidence supports its use in other depressive disorders. [35]
Selective Serotonin Reuptake Inhibitors
Class Summary
SSRIs potentiate the pharmacologic effects of serotonin (5-hydroxytryptamine [5-HT]) in the central nervous system (CNS).
Citalopram (Celexa)
Citalopram is an SSRI used to treat depression. It is similar to fluoxetine, sertraline, and paroxetine. A highly selective reuptake inhibitor of serotonin, citalopram has little effect on other neurotransmitters.
Fluvoxamine (Luvox CR)
Fluvoxamine is a potent selective inhibitor of neuronal serotonin reuptake. It does not significantly bind to alpha-adrenergic, histamine, or cholinergic receptors and thus has fewer adverse effects than do tricyclic antidepressants. Fluvoxamine was approved initially for OCD but is effective in dysthymia.
Paroxetine (Paxil, Pexeva)
Paroxetine is a potent selective inhibitor of neuronal serotonin reuptake. It also has a weak effect on norepinephrine and dopamine neuronal reuptake. For maintenance therapy, adjust the dosage to maintain the patient on the lowest effective dosage, and reassess the patient periodically to determine the need for continued treatment, as is true for all SSRIs.
Fluoxetine (Prozac)
Fluoxetine, the best-studied drug, has a long half-life. It selectively inhibits presynaptic serotonin reuptake with minimal or no effect on the reuptake of norepinephrine or dopamine.
Sertraline (Zoloft)
Sertraline selectively inhibits presynaptic serotonin reuptake.
Escitalopram (Lexapro)
Escitalopram is an SSRI and an S-enantiomer of citalopram. It is used for the treatment of depression. The drug's mechanism of action is thought to be the potentiation of serotonergic activity in the CNS resulting from the inhibition of CNS neuronal reuptake of serotonin.
Tricyclic Antidepressants
Class Summary
The tricyclics are the prototypical antidepressants. Their anticholinergic (dry mouth) and antihistaminic (sedating) effects make noncompliance more of a problem than with the newer drugs. This is particularly a problem when the depressive symptoms are relatively mild. However, their very broad-based actions on a variety of neurotransmitters make them effective on occasions when SSRIs fail. Adverse effects with the so-called second-generation drugs generally are less of a problem.
Nortriptyline (Pamelor)
Nortriptyline has demonstrated effectiveness in the treatment of chronic pain. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration of these neurotransmitters in the CNS. Pharmacodynamic effects such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play a role in its mechanisms of action.
Desipramine HCl (Norpramin)
Desipramine HCL may increase the synaptic concentration of norepinephrine in the CNS by inhibiting reuptake of norepinephrine by the presynaptic neuronal membrane. It may have effects in the desensitization of adenyl cyclase, down-regulation of beta-adrenergic receptors, and down-regulation of serotonin receptors.
Antidepressants, Other
Class Summary
The mixed serotonergic and noradrenergic drugs have effects on serotonin, norepinephrine, and, in some cases, dopamine and even on nicotinic acetylcholine systems. Because of the empirical nature of psychopharmacology, they may be used as first-line drugs or as follow-up agents when SSRIs fail.
Duloxetine (Cymbalta)
Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake. Its antidepressive action is theorized to be due to serotonergic and noradrenergic potentiation in the CNS.
Bupropion (Wellbutrin, Budeprion SR, Budeprion XL, Wellbutrin SR)
Bupropion inhibits neuronal dopamine reuptake, but it is also a weak blocker of serotonin and norepinephrine reuptake. A low incidence of sexual dysfunctions occurs with this medication. Bupropion binds to the nicotinic receptor and helps with smoking cessation.
Mirtazapine (Remeron, Remeron SolTab)
Mirtazapine is an antidepressant that is not chemically related to the tricyclics or to any other class of antidepressants. Its primary mechanism of action is antagonism at the central presynaptic alpha-2 receptors. The actions of the drug change as the dose is raised. Mirtazapine exhibits noradrenergic and serotonergic activity.
Venlafaxine (Effexor, Effexor XR)
Venlafaxine is structurally unrelated to other available antidepressants. It inhibits serotonin reuptake at select receptors, as well as the reuptake of norepinephrine.
Thyroid Products
Class Summary
These drugs are administered as an augmentation strategy. They may convert nonresponders (to antidepressants) to responders by increasing receptor sensitivity and enhancing the effects of antidepressants, particularly tricyclic antidepressants.
T3, liothyronine (Cytomel, Triostat)
Liothyronine is a synthetic form of natural thyroid hormone T3 converted from T4. Its duration of activity is short and allows for quick dosage adjustments in the event of overdosage. Liothyronine may need to be administered as often as 4 times daily. In its active form, the drug influences the growth and maturation of tissues.
The dose should be one quarter of the T4 dose, according to some; others recommend administering liothyronine alone.
T3/T4 combinations (Armour Thyroid, Westhroid, Nature-Throid)
These are mixtures of 1 part T3 to 4 parts T4; they carry the same advice and warnings that the 2 hormones do when administered separately. For desiccated thyroid, 1 grain (60 mg) contains 38 mcg T4 and 9 mcg T3. Thyrolar 1 contains 50 mcg T4 and 12.5 mcg T3.
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The various outcomes of dysthymia.
