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The Need for Better Management of Treatment-Resistant Depression, Part 3:
Better Ways to Manage Treatment-Resistant Depression
David L. Dunner, M.D.

Rating Scales for Depression
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American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depressive Disorder [Revision]. Am J Diagnostic Criteria
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: Duration
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Augmenting Agents
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Joffe RT. Triiodothyronine potentiation of fluoxetine in depressed patients. Can J Psychiatry 1992;37:48–50 Bauer MS, Whybrow PC. Rapid cycling bipolar affective disorder, 2: treatment of rapid cycling with high-dose levothyroxine: a preliminary study. Arch Gen Psychiatry 1990;47:435–440 Targum SD, Greenberg RD, Harmon RL, et al. Thyroid hormone and the TSH stimulation test in refractory depression. J Clin Psychiatry Goodwin FK, Prange AJ Jr, Post RM, et al. Potentiation of antidepressant effects by L-triiodothyronine in tricyclic nonresponders. Am J Psychiatry 1982;139:34–38 Atypical Neuroleptics
Dunner DL, Amsterdam JD, Shelton RC. Adjunctive ziprasidone in treatment-resistant depression: a pilot study [poster]. Presented at the 43rd annual meeting of the New Clinical Drug Evaluation Unit; Shelton RC, Tollefson GD, Tohen M, et al. A novel augmentation strategy for treating resistant major depression. Am J Psychiatry Ostroff RB, Nelson JC. Risperidone augmentation of selective serotonin reuptake inhibitors in major depression. J Clin Psychiatry Benzodiazepines
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Bader GM, Hawley JM, Short DD. Venlafaxine augmentation with methylphenidate for treatment-refractory depression: a case report.
Masand PS, Anand VS, Tanquary JF. Psychostimulant augmentation of second generation antidepressants: a case series. Depress Anxiety Fawcett J, Kravitz HM, Zajecka JM, et al. CNS stimulant potentiation of monoamine oxidase inhibitors in treatment-refractory depression.
Barbosa L, Berk M, Vorster M. A double-blind, randomized, placebo- controlled trial of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes. J Clin Psychiatry 2003;64:403–407 Rocha FL, Hara C. Lamotrigine augmentation in unipolar depression.
Barbee JG, Jamhour NJ. Lamotrigine as an augmentation agent in treatment-resistant depression. J Clin Psychiatry 2002;63:737–741 Normann C, Hummel B, Schärer LO, et al. Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled, double-blind study. J Clin Psychiatry 2002;63:337–344 Buspirone
Appelberg BG, Syvälahti EK, Koskinen TE, et al. Patients with severe depression may benefit from buspirone augmentation of selective serotonin reuptake inhibitors: results from a placebo-controlled, randomized, double-blind, placebo wash-in study. J Clin Psychiatry Landén M, Björling G, Agren H, et al. A randomized, double-blind, placebo-controlled trial of buspirone in combination with an SSRI in patients with treatment-refractory depression. J Clin Psychiatry Dimitriou EC, Dimitriou CE. Buspirone augmentation of antidepressant therapy. J Clin Psychopharmacol 1998;18:465–469 Tryptophan
Tryptophan is no longer marketed in the United States.
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Thase ME, Blomgren SL, Birkett MA, et al. Fluoxetine treatment of patients with major depressive disorder who failed initial treatment with sertraline. J Clin Psychiatry 1997;58:16–21 Focus on Atypical Neuroleptic Augmentation of SSRIs
Risperidone Augmentation of Fluoxetine or
Ostroff RB, Nelsen JC. Risperidone augmentation of selective serotonin reuptake inhibitors in major depression. J Clin Psychiatry Olanzapine Augmentation of Fluoxetine
Shelton RC, Tollefson GD, Tohen M, et al. A novel augmentation strategy for treating resistant major depression. Am J Psychiatry Ziprasidone Augmentation of Sertraline
Dunner DL, Amsterdam JD, Shelton RC. Adjunctive ziprasidone in treatment-resistant depression: a pilot study [poster]. Presented at the 143rd annual meeting of the New Clinical Drug Evaluation Unit; Risperidone Augmentation of Citalopram
Rapaport MH, Canuso CM, Loescher A, et al. Preliminary results from the ARISe-D (risperidone augmentation in resistant depression)trial. In: New Research Abstracts of the 156th Annual Meeting ofthe American Psychiatric Association; May 19, 2003; San Francisco,Calif. Abstract NR179:66 How Atypical Neuroleptic Augmentation of SSRIs
May Improve Depression
Monoamine Receptor Hypothesis
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on Monoamines in the Rat Prefrontal Cortex
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Neuropsychopharmacology 2000;23:250–262 New Treatment Approaches
New Electrotherapies
High-Dose Right Unilateral (RUL) Electroconvulsive
Therapy (ECT)
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Neuropsychopharmacology 2003;28:1852–1865 Deep Brain Stimulation
Mayberg HS, Lozano AM, Voon V, et al. Deep brain stimulation for treatment-resistant depression. Neuron 2005;45:651–660 New Medications
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Benedictis E. 20mg transdermal selegiline daily may be effective and well tolerated in adults with major depression. Evid Based Ment Amsterdam JD. A double-blind, placebo-controlled trial of the safety and efficacy of selegiline transdermal system without dietary restrictions in patients with major depressive disorder. J Clin Bodkin JA, Amsterdam JD. Transdermal selegiline in major depression: a double-blind, placebo-controlled, parallel-group study in outpatients. Am J Psychiatry 2002;159:1869–1875 Other New Medications
Kramer MS, Winokur A, Kelsey J, et al. Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist inmajor depression. Neuropsychopharmacology 2004;29:385–392 Ranga K, Krishnan R. Clinical experience with substance P receptor (NK1) antagonists in depression. J Clin Psychiatry 2002;63(suppl 11):25–29 Steinberg R, Alonso R, Griebel G, et al. Selective blockade of neurokinin-2 receptors produces antidepressant-like effects associated with reduced corticotropin-releasing factor function.
Kramer MS, Cutler N, Feighner J, et al. Distinct mechanism for antidepressant activity by blockade of central substance P Corticotropin Releasing Factor (CRF) Antagonists Kunzel HE, Zobel AW, Nickel T, et al. Treatment of depression with the CRH-1-receptor antagonist R121919: endocrine changes and side effects. J Psychiatr Res 2003;37:525–533 O'Brien D, Skelton KH, Owens MJ, et al. Are CRF receptor antagonists potential antidepressants? Hum Psychopharmacol 2001;16:81–87 Mansbach RS, Brooks EN, Chen YL. Antidepressant-like effects of CP-154,526, a selective CRF1 receptor antagonist. Eur J Pharmacol Sequenced Treatment Alternatives to Relieve
Depression (STAR*D)
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