Treatment resistance depression

Vagus nerve stimulation (VNS) may be used for adult patients with treatment-resistant depression. A pulse generator is surgically implanted under the skin of the left chest, and an electrical lead connects the generator to the left vagus nerve. Stimulation of this nerve sends signals to the brain. This therapy is intended to be used along with traditional therapies, such as pharmacotherapy and ECT.20... 

Fava M. Augmentation and combination strategies in treatment-resistant depression. J Clin Psychiatry 2001 62(suppl 18) 4—11. 

Optimize the dose of mood stabilizing medication(s) before adding on lithium, lamotrigine, or antidepressant (e.g., bupropion or an SSRI) if psychotic features are present, add on an antipsychotic ECT used for severe or treatment-resistant depressive episodes or for psychosis or catatonia... 

Treatment-resistant depression Depression characterized by multiple failed trials of antidepressants and/or electroconvulsive therapy. 

Chen, J., Lu, Z., Jiang, S. D. et al. (2005). Association between polymorphism in the cytochrome P450 enzymes 1A2 2C19 gene and treatment-resistant depression. Shanghai Archive of Psychiatry, 17(2), 95-8. 

Amsterdam JD, Maislin G, Potter L. Fluoxetine efficacy in treatment resistant depression. Prog Neuropsychopharmacol Biol Psychiatry 1994 18 243-261. 

Most treatment-resistant depressed patients have received inadequate therapy. Issues to be considered in patients who have not responded to treatment include the following (1) Is the diagnosis correct (2) Does the patient have a psychotic depression (3) Has the patient received an adequate dose and duration of treatment (4) Do adverse effects preclude adequate dosing (5) Has the patient been compliant with the prescribed regimen (6) Was treatment outcome measured adequately (7) Is there a coexisting or preexisting medical or psychiatric disorder (8) Was a stepwise approach to treatment used (9) Are there other factors that interfere with treatment ... 

Alternatively, the current antidepressant may be augmented (potentiated) by the addition of another agent (e.g., lithium, T3), or an atypical antipsychotic (e.g., risperidone). Risperidone has been shown to be effective in combination with fluvoxamine, paroxetine, or citalopram in treatment-resistant depression. Olanzapine and fluoxetine have been found to be safe and effective in treatment-resistant depression. 

Triple reuptake inhibitors (TRIs), which inhibit reuptake at all three transporters, have attracted considerable interest in recent years [77]. The involvement of dopamine reuptake in the etiology of depression and other CNS disorders has been recognized [29,30]. As a result, TRIs have been proposed to offer a faster onset of action and improved efficacy for depression over currently prescribed single or dual action monoamine reuptake inhibitors. Historically, the mesocorticolimbic dopamine pathway is thought to mediate the anhedonia and lack of motivation observed in depressed patients [78,79]. In addition, methylphenidate, both immediate release and extended release formula, has been found to be effective as an augmenting agent in treatment-resistant depression [4]. Furthermore, clinical studies using the combination of bupropion and an SSRI or SNRI have showed improved efficacy for the treatment of MDD in patients refractory to the treatment with SSRIs, SNRIs, or bupropion alone [5,80,81]. 

The initial choice of therapy is also dictated by the severity of the depression (e.g., the severity of depressive symptoms impedes an adequate trial of psychotherapy), subtype of depression (e.g., presence of psychosis, seasonal depression, or treatment-resistant depressions) presence of comorbid disorders, prior treatment history, child and parent motivation toward treatment, and the clinician s motivation and expertise in implementing any specific intervention. 

Case reports have suggested that adding stimulant medications or combining a SSRI and a TCA or bupropion may also be effective (APA, 2000), but these combinations need to be done with caution, given the possibility of drug interactions (e.g., SSRIs cytochrome inhibition leading to toxic TCA levels). Additionally, in adults, the combination of antidepressants and psychotherapy (CBT, IPT) for patients with severe or treatment-resistant depression has been found useful (APA, 2000 Keller et al., 2000). 

Some randomized control trials have shown that TMS is efficacious and safe for the treatment of adults with MDD (with and without treatment-resistant depressions) (e.g., Grunhaus et ah, 2000 Martis and Jan-icak, 2000). However, the use of TMS has not been standardized and there is controversy regarding the methodology used in some studies. 

Poirier, M.F. and Boyer, P. (1999) Venlafaxine and paroxetine in treatment-resistant depression double-blind, randomized comparison. Br J Psychiatry 175 12-16. 

TABLE 18-3. Medical illnesses associated with treatment-resistant depression... 

NOVEL TREATMENT STRATEGIES FOR TREATMENT-RESISTANT DEPRESSION... 

Addition of the steroid suppressant aminoglutethimide to treatment with fluoxetine led to significant improvement in a case of treatment-refractory OCD [Chouinard et al. 1995]. The rationale for this approach was based on evidence that steroids contribute to the maintenance of the depressed mood state and that steroid-suppressant agents may be useful in cases of treatment-resistant depression. 

Amsterdam JD, Homig-Rohan M Treatment algorithms in treatment-resistant depression. Psychiatr Clin North Am 19 371-386, 1996 Amsterdam JD, Mozley PD Temporal lobe asymmetry with iofetamine (IMP) SPECT imaging in patients with major depression. J Affect Disord 24 43-53, 1992... 

Fava M High-dose fluoxetine in the treatment of depressed patients not responsive to a standard dose of fluoxetine. J Affect Disord 25 229-234, 1992 Fava M, Davidson KG Definition and epiemiology of treatment-resistant depression. 

Fawcett J Progress in treatment resistant depression we have a long way to go. Psychiatric Annals 24 214-216, 1994... 

Feighner JP, Herbstein J, Damlouju N Combined MAOl, TCA and direct stimulant therapy of treatment resistant depression. J Chn Psychiatry 6 206-209, 1985 Feighner JP, Pambakian R, Fowler RC, et al A comparison of nefazadone, imipramine and placebo in patients with moderate to severe depression. Psychopharmacol Bull 25 219-221, 1989a... 

Hornig-Rohan M, Amsterdam JD Clinical and biological correlates of treatment-resistant depression an overview. J Clin Psychiatry 24 220-227, 1994 Horowski R, Wachtel L, Turski L, et al Glutamate excitotoxicity as a possible pathogenetic mechanism in chronic neurodegeneration, in Neurodegenerative Diseases. Edited by Caine DB. Philadelphia, PA, WB Saunders, 1994, pp 163-174... 

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