Antidepressants augmentation therapy

We have reviewed antidepressant augmentation strategies, including the principles and several specific examples. Finally, we have touched on the use of electroconvulsive therapy and psychotherapy for the treatment of depression. 

Modafinil is itself an augmenting therapy to antidepressants tor residual sleepiness and fatigue in major depressive disorder... 

Mood stabilizers can be used as augmentation therapy in cases of partial response to antidepressant therapy, especially those with prominent irritability or anger. Anticonvulsants (thought to exert their mechanism in part through antikindling effects) have been effective in treating PTSD. In a retrospective review topiramate reduced nightmares and flashbacks. Divalproex sodium was effective in an open trial. ... 

Lamotrigine is effective for the maintenance treatment of bipolar I disorder in adults. It has both antidepressant and mood-stabilizing effects, and it may have augmenting properties when combined with lithium or valproate. It has low rates of switching patients to mania. Although it is less effective for acute mania compared to lithium and valproate, it may be beneficial for the maintenance therapy of treatment-resistant bipolar I and II disorders, rapidcycling, and mixed states. It is often used for bipolar II patients. 

A recent open label retrospective report indicates that tiagabine, which acts by blocking GABA reuptake, might be an effective augmentation strategy for patients who are only partially responsive to antidepressant therapy. 

An adequate trial of antidepressant medication is defined as treatment with therapeutic doses of a drug for a total of 4 weeks. After 4 weeks of antidepressant treatment, patients can be divided into three groups those who have achieved a full response, those who have achieved a partial response, and those who have not responded. In the case of patients who achieve full remission, treatment should continue for a minimum of 4-6 months, or longer if the patient has a history of recurrent depression (see Maintenance Treatment of Major Depression later in this chapter). If a partial response has been achieved by 4 weeks, a full response may be evident within an additional 2 weeks without further intervention. If the symptoms do not respond at all, the dose should be increased, a different antidepressant should be used, or the therapy should be augmented with another medication (see Treatment-Resistant Depression later in this chapter). 

Stimulants such as amphetamine and methylphenidate have been used to treat depression for many years. Stimulants should not be used alone, except perhaps in geriatric patients with prominent apathy, medically ill patients with depression, or patients with poststroke depression (Lingam et al. 1988). However, psychostimulants are useful for augmentation of antidepressant therapy in refractory depression, and they are generally safe, even for most patients with cardiac disorders. The nonamphetamine stimulant modafmil was found to be helpful in a recent placebo-controlled study involving 311 patients with partial response to SSRIs (Fava et al. 2005). 

A normal response is an increase in plasma TSH of 5 to 15 pU/mL above baseline. A response of less than 5 pU/mL above baseline is generally considered to be blunted (some laboratories consider a response below 7 pU/mL to be blunted) and may be consistent with a major depression. An abnormal test is found in approximately 25% of patients with depression. A blunted TSH response (especially in conjunction with an abnormal DST) may help in confirming the differential diagnosis of a major depressive episode and support continued antidepressant treatment. An increased baseline TSH or an augmented TSH response (higher than 30 pU/mL), in conjunction with other thyroid indices, might identify patients with hypothyroidism, mimicking a depressive disorder. These patients may benefit most from thyroid replacement therapy. 

Lithium Lithium augmentation of standard antidepressants has been reported to significantly benefit previously treatment-resistant and psychotic depressions, particularly in bipolar patients ( 371, 372). There is substantial case report literature reporting that many patients have benefited when lithium was added to ongoing TCA therapy. Often these results occurred rapidly, sometimes with low doses of lithium. Although the results of controlled trials have not been as dramatic, they still support this approach, which should be seriously considered for treatment-resistant major depression. 

Orengo CA, Fullerton L, Kunik ME. Safety and efficacy of testosterone gel 1% augmentation in depressed men with partial response to antidepressant therapy. J Geriat Psychiatry Neurol 2005 18 20-4. 

A double-blind, placebo-controlled trial of the use of lithimn to augment antidepressant medication for treating unipolar major depression has shown it to be beneficial for patients receiving continuation therapy following acute therapy for a major depressive episode. The 14 patients in the lithium-treated group suffered no relapses over 4 months, while seven of the 15 patients in the placebo-treated group experienced relapses including one suicide. ... 

Patients taking certain systemic medications are also more sensitive to the pressor effects of phenylephrine. In individuals taking atropine, the pressor effect of phenylephrine is augmented, and tachycardia can occur. Tricyclic antidepressants and monoamine oxidase (MAO) inhibitors also potentiate the cardiovascular effects of topical phenylephrine. The concomitant use of phenylephrine is contraindicated with these agents, even up to 21 days after cessation of MAO inhibitor therapy. Similarly, patients taking reserpine, guanethidine, or methyldopa are at increased risk for adverse pressor effects from topical phenylephrine because of denervation hypersensitivity accompanying the chemical sympathectomy. 

Results of low-dose risperidone (0.5 to 2 mg/day) added to antidepressant therapy in refractory patients are encouraging. Treatment response over 6 weeks was rapid and consistent. An additional 8-week, open-label study reported that 50% of patients previously unresponsive to clomipramine responded after risperidone 3 mg/day was added. The recommended initial dose of risperidone is 0.25 mg, and the target dose is 0.5 to 5 mg/day. Thirty-six patients unresponsive to antidepressants were given risperidone, up to 6 mg/day or placebo in a double-blind trial. Risperidone treatment resulted in a significant reduction in YBOCS scores. " In an open-label trial of olanzapine augmentation of SSRIs for 8 weeks, most patients experienced complete or partial remission in doses of 1.25 to 20 mg/day. ... 

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