Selective serotonin reuptake inhibitors olanzapine

Weiss EL, Potenza MN, McDougle CJ, et al. Olanzapine addition in obsessive-compulsive disorder refractory to selective serotonin reuptake inhibitors an open-label case series. J Clin Psychiatry 1999 60 524-527. 

The depressive phase of manic-depressive disorder often requires concurrent use of an antidepressant drug (see Chapter 30). Tricyclic antidepressant agents have been linked to precipitation of mania, with more rapid cycling of mood swings, although most patients do not show this effect. Selective serotonin reuptake inhibitors are less likely to induce mania but may have limited efficacy. Bupropion has shown some promise but—like tricyclic antidepressants—may induce mania at higher doses. As shown in recent controlled trials, the anticonvulsant lamotrigine is effective for many patients with bipolar depression. For some patients, however, one of the older monoamine oxidase inhibitors may be the antidepressant of choice. Quetiapine and the combination of olanzapine and fluoxetine has been approved for use in bipolar depression. 

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. 

Marangell LB, Johnson CR, Kertz B, Zboyan HA, Martinez JM. Olanzapine in the treatment of apathy in previously depressed participants maintained with selective serotonin reuptake inhibitors an open-label, flexible-dose study. J Clin Psychiatry 2002 63(5) 391-5. 

Olanzapine, mean dose 5.4 mg/day, has been given to 21 patients with apathy in the absence of depression after long-term treatment with selective serotonin reuptake inhibitors for non-psychotic depression in an open, flexible-dose study (16). The more frequent adverse effects were sedation (n = 12), increased appetite (n = 8), stiffness (n = 7), edema (n = 6), and dry mouth (n = 5). 

Olanzapine was effective in an open trial in 10 patients with obsessive-compulsive disorder refractory to selective serotonin reuptake inhibitors, who were given additional olanzapine they had minimal adverse effects, primarily sedation (27). 

There have been reports that selective serotonin reuptake inhibitors, which inhibit CYP1A2, increase plasma olanzapine concentrations (SEDA-24, 71 SEDA-26, 63). In a recent open add-on trial, 21 patients with obsessive-compulsive disorder unresponsive to treatment with paroxetine 60 mg/day for at least 12 weeks, took additional olanzapine 10 mg/day (280). Steady-state plasma concentrations of paroxetine were not changed, and 7 patients were rated as responders at final evaluation. Sedation (n = 12), weight gain up to 3 kg (n = 8), dry mouth (n = 6), and constipation (n = 3) were the most frequent adverse effects. 

Haloperidol (Haldol), risperidone (Risperdal), loxapine (Loxitane), ziprasidone (Geodon), quetiapine (Seroquel), clozapine (Clozaril), aripiprazole (Abilify), and thioridazine (Mellaril) are targeted in this solid phase extraction (SPE), liquid chromatography— tandem mass spectrometry (LC-MS/MS) method. Both 9-hydroxy-risperidone (Paliperiodone), an equipotent metabolite, and mesoridazine (Serentil) are also included in this method as they are pharmacologically active major metabolites of risperidone and thioridazine, respectively (4). Olanzapine (Zyprexa) can be quantified with this instrument method however, the extraction method is a liquid-liquid basic extraction (see Note 1). Due to the subsequent administration of antidepressants in conjunction with antipsychot-ics, this method can also be used for many of the common antidepressants, including the selective serotonin reuptake inhibitors (SSRIs) (see Note 2). 

Thiophene seems to be very popular in Li Lilly drugs. Its dual selective serotonin and norepinephrine reuptake inhibitor (SSNRI) for depression, duloxetine (Cymbalta), contains a thiophene. And its atypical antipsychotic drug olanzapine (Zyprexa) has a fused thiophene as its core structure. 

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