Fluoxetine refractory

Shapira NA, Ward HE, Mandoki M, Murphy TK, Yang MCK, Blier P, Goodman WK. A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder. Biol Psychiatry 2004 55 553-5. 

MAOIs are reserved for the most difficult or refractory panic disorder patients. Side effects and dietary and drug restrictions affect patient acceptance (see Chap. 70 for food and drug restrictions). Fluoxetine must be stopped 5 weeks before phenelzine (or another MAOI) is started. Other antidepressants should be stopped 2 weeks before phenelzine is started. 

Olanzapine (Zyprexa). The olanzapine molecule is structurally very similar to clozapine and therefore exerts very similar effects on brain receptors. The dose range of olanzapine for treating schizophrenia is from 5 to 30mg/day. Like clozapine, olanzapine appears to treat both positive and negative symptoms. It is also approved for the treatment of the manic phase of bipolar disorder. It has also been shown to augment the antidepressant effects of fluoxetine in refractory patients. 

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. 

Jenike MA, Baer L, Buttolph L Buspirone augmentation of fluoxetine in patients with obsessive compulsive disorder. J Clin Psychiatry 52 13-14, 1991a Jenike MA, Baer L, Ballantine HT, et al Cingulotomy for refractory obsessive-compulsive disorder a long-term follow-up of 33 patients. Arch Gen Psychiatry 48 548-555, 1991b... 

Although the efficacy of tricyclic antidepressants in the treatment of unipolar depression is beyond reproach, the side-effect profile of these agents makes them less desirable as first-line therapeutic agents. Introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine in the past decade has revolutionized the treatment of depression universally. The side-effect profile of SSRIs, such as nausea, diarrhea and sexual dysfunction, is considerably more benign than that of tricyclic drugs. Multiple controlled trials have proven the efficacy of SSRIs vs. placebo (Nemeroff, 1994). Recently, a number of SNRIs (serotonin and noradrenaline reuptake inhibitors) and so-called atypical antidepressants have been marketed that may have additional advantages over SSRIs, such as more rapid onset of action (venlafaxine. mirtazapine) and low sexual side-effect potential ( bupropion, nefazodone). Additionally, it appears that venlafaxine may be more efficacious in cases of treatment-refractory depression (Clerc et al., 1994 Fatemi et al., 1999). Finally, in a recent report (Thase et al., 2001),... 

Pope HG, McElroy SL, Nixon RA. Possible synergism between fluoxetine and lithium in refractory depression. Am J Psychiatry 1988 145 1292-1294. 

MAOIs, TCAs, lithium, clomipramine (alone or with topical steroids), fluoxetine, and fluvoxamine may reduce the frequency and intensity of this disorder ( 210, 226, 255, 256, 257, 258, 259, 260 and 261) however, controlled trials are needed to conclusively establish efficacy. Relapse after initial improvement has also been reported, however. Data also indicate that both trichotillomania and OCD may respond to venlafaxine ( 262, 263). For children, such treatments should be reserved for only those with the more severe, refractory forms. 

Recent case reports have suggested that atypical antipsychotics may also benefit patients with PTSD. For example, low doses of risperidone in combination with an antidepressant or mood stabilizer were reported effective for nightmares and flashbacks in patients with treatment-refractory PTSD ( 292). Both clozapine and olanzapine have also been reported to reduce PTSD symptoms in patients with a co-morbid psychotic disorder ( 293, 294). Finally, olanzapine added to fluoxetine resulted in significant improvement of hyperarousal symptoms in a patient with treatment-refractory PTSD caused by severe childhood physical and sexual abuse (295). 

Cornelius JR, Soloff PH, Perel JM, et al. A preliminary trial of fluoxetine in refractory borderline patients. J Clin Psychopharmacol 1991 11 116-120. 

Improvement in galactorrhea has also been observed in a case of trichotillomania refractory to a selective serotonin reuptake inhibitor (857). The patient only had a positive response with risperidone in combination with fluoxetine, but developed hyperprolactinemia and an intolerable galactorrhea. Olanzapine in combination with fluoxetine was started, with significant clinical improvement and without symptoms of galactorrhea however, the patient had undesired weight gain of 3.6 kg after 22 weeks. 

Well accepted for use in schizophrenia and bipolar disorder, including difficult cases Documented utility in treatment-refractory cases, especially at higher doses Documented efficacy as augmenting agent to SSRIs (especially fluoxetine) in nonpsychotic treatment-resistant major depressive disorder Documented efficacy in bipolar depression, especially in combination with fluoxetine... 

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