Treatment-refractory patients

To date, clozapine remains the only drug with proven and superior efficacy in treatment-resistant patients, and it is currently the only drug approved for the treatment-resistant schizophrenic. Studies have shown a response of approximately 30% to 50% in these well-defined treatment-resistant patients. Clinical trials have consistently found clozapine to be superior to traditional antipsychotics for treatment-refractory patients, and it is efficacious even after nonresponse to other SGAs and in partially responsive patients. It is often rapidly effective even in those who have had a poor response to other medication for years. Recent studies have demonstrated that it has a beneficial effect for aggression and suicidality, which led to the Food and Drug Administration (FDA) approval for the treatment of suicidal behavior in people with psychosis.41... 

The MAOI phenelzine and the RIMAs brofaramine and meclobemide are effective in SAD. Phenelzine is effective in 64% to 69% of SAD patients.58 It is generally reserved for treatment-refractory patients owing to dietary restrictions,... 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

Much of the time, treatment-extant literature doesn t provide much guidance when the patient has multiple comorbidities or already has failed best-practice initial interventions. The few available comparative treatment trials that include both medication and psychotherapy all focus on acute treatment or, less commonly, the heroic management of treatment-refractory patients. This leaves out the majority of patients for whom combined treatment is appropriate if not de rigueur, namely those who are partial responders to initial treatment and/or who require a combination of treatments because of comorbidity. Furthermore, for many clinically important decisions, it is unlikely that there will ever be randomized evidence. For example, how many SSRI trials should precede a clomipramine trial in the partially responsive child with OCD Flow long does one wait before adding a SSRI when treating a child with OCD who is not particularly responsive to weekly CBT ... 

Faedda GL, Baldessarini RJ, Tohen M, et al Episode sequence in bipolar disorder and response to lithium treatment. Am J Psychiatry 148 1237-1239, 1991 Falkenburg T, Mohammed AK, Henriksson B, et al Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment. Neurosci Lett 138 153-156, 1992 Fallon BA, Campeas R, Schneier FR, et al Open trial of intravenous clomipramine in five treatment-refractory patients with obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci 4 70-75, 1992... 

Quitkin F, Rifkin A, Klein DF. Very high dosage vs. standard dosage fluphenazine in schizophrenia a double-blind study of nonchronic treatment-refractory patients. Arch Gen Psychiatry 1975 32 1276-1281. 

Bauer et al. (126) entered 11 rapid-cycling, treatment-refractory patients into an open trial of high-dose levothyroxine sodium, added to their previously stabilized medication regimen. The dosage of the levothyroxine was increased by 0.05 to 0.1 mg/day every 1 to 2 weeks, as tolerated, until symptoms improved or adverse effects prevented further increases. Scores on both the depressive and the manic symptom rating scales decreased significantly compared with baseline scores. 

Of the two types of resistance identified, aerobic resistance is of clinical importance as most clinical isolates from treatment-refractory patients show resistance of this type. However, findings regarding the stepwise development of resistance, and continuity of resistance development from the aerobic to the anaerobic type, point to the possibility that I vaginalis strains at the early stage of anaerobic resistance could also appear in the field. In fact, some isolates reported from Upcroft s laboratory (Dunne al. 2004) and occasional isolates from surveys (e.g., Lossick et al. 1987) displaying high aerobic MLC... 

Twenty years ago, a classic study demonstrated that 30% of treatment-refractory patients who did not respond to other antipsychotics responded to clozapine [73]. Meta-analyses have consistently demonstrated that clozapine may be the most efficacious antipsychotic [74]. The development of a genetic test that would predict the likelihood of response to clozapine would increase the number of patients who could benefit from this drug at an earlier stage. 

Gupta S, Masand PS, Frank B et al. Topiramate in bipolar and schizoaffective disorder mood stabilizing properties in treatment refractory patients. XXII Collegium Internationale Neuropsychopharmacologicum Conference, Brussels, Belgium, July 2000. 

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