Partial responder

Antiadrenergic drugs (prazosin) can be useful in some patients with PTSD, and antipsychotics (risperidone, quetiapine, and olanzapine) may be used as augmenting agents in partial responders. 

The practice guideline of the American Psychiatric Association recommends that after 6 to 8 weeks of antidepressant treatment, partial responders should consider changing the dose, augmenting the antidepressant, or adding psychotherapy or ECT. For those with no response, options include changing to another antidepressant or the addition of psychotherapy or ECT. 

In partial responders who are tolerating the antipsychotic well, it may be reasonable to titrate above the usual dose range. 

Despite its considerable efficacy, clomipramine has given way to the SSRls as a result of their more favorable side effect and safety profiles. Clomipramine, however, is often used as an augmenfafion sfrategy for OCD pafienfs who are partial responders to SSRl therapy. The effectiveness of this approach has not been verified in confrolled frials. Furthermore, coadministration of clomipramine with some of the SSRls can result in potentially dangerous drug interactions. 

Pindolol (Visken). A beta blocker known to potentiate serotonin activity via a distinct action on serotonin autoreceptors, pindolol has been reported in a controlled study to augment SSRl treatment in OCD patients who are partial responders. Pindolol is administered at a dose of 2.5 mg three times daily. It is generally well tolerated but low blood pressure, dizziness, and sedation can occur. 

The Phase I studies of vindesine determined the maximum tolerated dose of the compound to be 3-4 mg/m (body surface area) when given once weekly (i.v.) 78). Mild leukopenia ensues, reaching a nadir after about 4 days, and is accompanied by neurotoxicity. Several patients responded to drug treatment during this initial trial, including several complete responders with acute leukemias and partial responders with malignant melanoma and non-Hodgkin s lymphoma. Subsequent studies indicated that vindesine was active in vincristine-resistant childhood lymphocytic leukemia and, when combined with cisplatin, was effective in... 

Kies MS, Mira JG, Crowley JJ, etal. Multimodal therapy for limited small-cell lung cancer A randomized study of induction combination chemotherapy with or without thoracic radiation in complete responders, and with wide-field vs reduced-field radiation in partial responders A Southwest Oncology Group Study. J Clin Oncol 1987 5 592-600. 

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 ... 

Increasing the dosage. This strategy can be used for partial responders, but in occasional cases of patients with no response, increasing the dosage for another 2-3 weeks may help (APA, 2000). 

In this chapter, we focus on medical approaches to the patient with OCD who is either a nonresponder or a partial responder to treatment with SRls. (A review of the efficacy and use of SRls in OCD appears elsewhere in this volume.) The current state of knowledge regarding the efficacy of these approaches is summarized and recommendations are proposed based on empirical evidence and the clinical experience of the authors. The role of behavior therapy alone or in combination with SRls is mentioned, but a comprehensive discussion of this topic is beyond the scope of this chapter. The place of SRI monotherapy in nonresponders to behavior therapy is not addressed here, nor is evaluation of the adequacy of behavior therapy. 

Fava M, Judge R, Hoog SL, et al Fluoxetine versus sertraline and paroxetine in major depressive disorder changes in weight with long-term treatment. J Clin Psychiatry 61 863-867, 2000 Fava M, Thase ME, DeBattista C A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry 66 85-93, 2005... 

E. Therapeutic response In renal cell carcinoma studies, an objective response was seen in 15% of patients, with 7% complete and 8% partial responders. In metastatic melanoma studies, an objective response was seen in 16% of patients, with 6% complete and 10% partial responders. In patients with HIV infection, Proleukin increases the CD4 count, with no effect on viral load. 

There are several studies that combined lithium with other treatments such as antipsychotics, anticonvulsants (e.g., CBZ, VPA), calcium channel blockers (e.g., verapamil), or BZDs (e.g., lorazepam). Generally, in partial responders, the addition of these medications was beneficial and well tolerated. 

Defects of LDL receptors underlie this disorder. Some individuals have combined heterozygosity for alleles producing nonfunctional and kinetically impaired receptors. Levels of LDL in compliant heterozygous patients can be normalized with combined drug regimens (Figure 35-2). Those whose receptors retain even minimal function may partially respond to resins or reductase inhibitors. Niacin and atorvastatin may benefit patients with no receptor function. 

Simon, J. S. Nemeroff, C. B. (2005). Aripiprazole augmentation of antidepressants for the treatment of partially responding and nonresponding patients with major depressive disorder. J. Clin. Psychiatry, 66, 1216-1220. 

Altamura AC, Velona I, Curreli R, Mundo E, Bravi D. Is olanzapine better than haloperidol in resistant schizophrenia A double-blind study in partial responders. Int J Psychiatry Clin Pract 2002 6 107-11. 

Responders to drug therapy should continue treatment for at least 12 months. When discontinued, drug therapy should be tapered slowly over a period of 1 month or more to reduce the likelihood of relapse. Antiadrenergic drugs (prazosin) can be useful in some patients with PTSD, and antipsychotics (risperidone, quetiapine, and olanzapine) may be used as augmenting agents in partial responders. 

Rather than raise the dose above these levels in partial responders, consider augmentation with a mood stabilizing anticonvulsant, such as valproate or lamotrigine... 

To augment partial responders to an atypical antipsychotic, consider doses of loxapine as low as 5-60 mg/day, but use full doses if necessary... 

Enhances efficacy in clozapine partial responders when given concomitantly with clozapine... 

Similar findings have been reported in patients, with several studies showing that in patients who failed to respond to conventional AmB, or develop nephrotoxicity, had either a complete or partial responders to lipid formulation of AmB, without associated deterioration in renal funchon [128,156-159,161,162, 164], and recently it has been shown that induction of human monocytes by AmB, ABCD, ABLC and L-Amph leads to a differential expression of cytokines and chemokines. This differential inflammation could be contributing to the difference in efficacy and toxicity of AmB and its related lipid based formulations [171]. 

Of the 255 patients used for the revised application, 28 (11 percent) were classified as partial responders, meaning that their tumors had shrunk by half or more, and existing lesions had not expanded in size. FDA officials were convinced by this measure of Proleukin s efficacy. They even reproduced Chiron s data in their Summary for Basis of Approval Seven of the 28 partial responders and none of the complete responders were symptomatic from their disease (PS=i) at study entry. Of these seven patients, one returned to baseline after therapy and the other six became asymptomatic (PS=o). 18 Between the ECOG status and uncertainties in how to define partial and "complete responses, proof of efficacy, now more than ever, required patient assessment and communication between physicians and patients in the clinical trial. Furthermore, the company and FDA officials had to negotiate appropriate measures of efficacy and how to scale data from various tests. 

When they occur, depressive symptoms should be treated actively using a combination of cognitive-behavioral therapy and an antidepressant drug. Of the available antidepressants, selective serotonin reuptake inhibitors (SSRIs) have the most favourable combination of efficacy and side-effect profile for the elderly, regardless of the presence of medical co-morbidities. Although the dual agent venlafaxine has been proposed as an alternative agent for older patients who are either non-responders or partial responders to SSRIs, the frail elderly may be particularly vulnerable to its side effects (Hayes 2004). 

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