Depressive disorders refractory patients

Karajgi B, Rifkin A, Doddi S, et al The prevalence of anxiety disorders in patients with chronic obstructive pulmonary disease. Am J Psychiatry 147 200-201, 1990 Karazman R, Konig G, Langer G, et al Narcotherapy in resistant depressive patients, in Refractory Depression [Advances in Neuropsychiatry and Psychopharmacology, Vol 2). Edited by Amsterdam JD. New York, Raven, 1991, pp 223-231... 

Lithium has been proven effective for acute and prophylactic treatment of both manic and depressive episodes in patients with bipolar illness (American Psychiatric Association 2002). However, patients with rapid-cycling bipolar disorder (i.e., patients who experience four or more mood disorder episodes per year) have been reported to respond less well to lithium treatment (Dunner and Fieve 1974 Prien et al. 1984 Wehr et al. 1988). Lithium is also effective in preventing future depressive episodes in patients with recurrent unipolar depressive disorder (American Psychiatric Association 2002) and as an adjunct to antidepressant therapy in depressed patients whose illness is partially refractory to treatment with antidepressants alone (discussed in Chapter 2). Furthermore, hthium may be useful in maintaining remission of depressive disorders after electroconvulsive therapy (Coppen et al. 1981 Sackeim et al. 2001). Lithium also has been used effectively in some cases of aggression and behavioral dyscontrol. 

In 27 children with refractory generalized convulsive status epilepticus, midazolam 0.2 mg/kg as a bolus followed by 1-5 (mean 3.1) micrograms/kg/minute as a continuous infusion achieved complete control of seizures in 26 children within 65 minutes (14). There were no adverse effects, such as hypotension, bradycardia, or respiratory depression. In one patient with acute meningoencephalitis, status epilepticus could not be controlled. Five patients died of the primary disorders, one with progressive encephalopathy. 

Electroconvulsive therapy (ECT) is probably the most effective treatment for major depressive disorder (MDD) with psychotic features, with average response rates of 70-90%, compared with only about 40% for regular antidepressant medications. The response rates for MDD without psychosis are comparable between regular medications and ECT (about 70-75%). ECT is usually given to patients whose condition is refractory to or who are intolerant of antidepressant medication. 

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]. 

Other Uses in Geriatric Patient Depression refractory to other measures, anxiety symptoms and related disorders... 

Given the use of venlafaxine for treatment-refractory depression in adults, it is likely that it will be used for similar purposes in children. In addition, it is likely that venlafaxine will be used for childhood anxiety disorders. It is unclear whether venlafaxine is serotonergi-cally powerful enough to be useful in OCD. The lack of significant drug-drug interactions may facilitate its use in patients for whom antidepressant medication combinations are anticipated. 

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). 

Other interventions used for refractory bipolar depressed patients include atypical antipsychotics, thyroid hormones, stimulants (often used in the treatment of attention-deficit/hyperactivity disorder), and phototherapy. Repetitive transcraneal magnetic stimulation (rTMS) and vagal nerve stimulation (VNS) are techniques currently being researched. 

Electroconvulsive therapy remains the gold standard for the treatment of major depression and a variety of other psychiatric and neurologic disorders (97). Because of the effectiveness and resurgence of ECT, more patients are considered to be good candidates for this treatment option. Overall, these patients are medication refractory and elderly and, thus, are more sensitive to polypharmacy. Additionally, these patients tend to have more coexisting medical problems. 

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