Olanzapine Clomipramine

When a satisfactory therapeutic response cannot be achieved with any single agent in conjunction with concomitant psychotherapy, augmentation strategies warrant consideration. Preferred augmentation strategies include (1) an atypical antipsychotic (risperidone, olanzapine), (2) clomipramine, (3) buspirone, and (4) pindolol. 

Antidepressants amitriptyline, clomipramine, imipramine, moclobemide, citalopram Antipsychotics olanzapine... 

Olanzapine Valproate Clomipramine Citalopram Isoflurane Clomipramine... 

Cyt 2D6 metabolizes haloperidol, risperidone, thioridazine, sertindole, olanzapine and clozapine common substrates - fluoxetine, paroxetine, sertraline, venlafaxine, amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, propranolol, metoprolol, timolol, codeine, encainide, flecanide. Common inhibitors - paroxetine, sertraline, fluoxetine. 

The seizures occurred in the presence of high concentrations of clomipramine in this case, suggesting a pharmacodynamic drug interaction, since neither agent given alone provoked seizure activity, whereas the combination did. It is, however, possible that clomipramine might have caused a rise in olanzapine blood concentrations, which were not measured. 

Clomipramine and olanzapine are both metabolized by CYP1A2 and CYP2D6, and it is therefore possible that raised concentrations of both compounds can result from co-administration. 

Seizures in a 34-year-old man were attributed to an interaction of olanzapine with clomipramine (190). 

Deshauer D, Albuquerque J, Alda M, Grof P. Seizures caused by possible interaction between olanzapine and clomipramine. J Clin Psychopharmacol 2000 20(2) 283 1. 

CYP1A2 Antidepressants amitriptyline, clomipramine, imipramine, fluvoxamine Neuroleptics haloperidol, phenothiazines, thiothixene, clozapine, olanzapine Others tacrine, caffeine, theophylline, acetaminophen, phenacetin No report of polymorphism until 1999 significance of following findings remains unclear 1C reduced activity 23% in Japanese 1F higher inducibility 32% in Caucasians... 

Results of low-dose risperidone (0.5 to 2 mg/day) added to antidepressant therapy in refractory patients are encouraging. Treatment response over 6 weeks was rapid and consistent. An additional 8-week, open-label study reported that 50% of patients previously unresponsive to clomipramine responded after risperidone 3 mg/day was added. The recommended initial dose of risperidone is 0.25 mg, and the target dose is 0.5 to 5 mg/day. Thirty-six patients unresponsive to antidepressants were given risperidone, up to 6 mg/day or placebo in a double-blind trial. Risperidone treatment resulted in a significant reduction in YBOCS scores. " In an open-label trial of olanzapine augmentation of SSRIs for 8 weeks, most patients experienced complete or partial remission in doses of 1.25 to 20 mg/day. ... 

Ajmaline, alprenolol, amiflamine, amphetamine, aprindine, captopril, chlorpheniramine, cinnarizine, citalopram, clomipramine, clozapine, codeine, desipramine, dolasteron, encainide, flecainide, fluoxetine, fluphenazine, haloperidol, hydrocordone, imipramine, loratidine, methoxyphenamine, 3,4-methylenedioxymethamphetamine, metoprolol, mexiletine, (S)- and (i )-mianserin, nifedipine, olanzapine, omeprazole, oxycodone, perhexiline, phenformin, propaphenone, propranolol, remoxipride, ritonavir, saquinavir, selegiline, tamsulosin, timolol, tomoxetine, tramadol, trifluperidol, zolpidem... 

Augmentation is called for when there is partial or non-response to the above approaches. Combinations of SSRIs with buspirone, clonazepam, clonidine, inositol, lithium, pindolol, olanzapine, risperidone, trazodone, tryptophan, and venlafaxine have been reported, with limited benefit. To date, only two augmenting agents have been found to be effective in double-blind studies risperidone and pindolol. Augmentation of SSRIs with clomipramine (or vice versa) is a common practice in non-responders however, this combination may lead to a substantial increase in the level of tricyclics in the blood and/or increase the risk of serotonin syndrome. Phenelzine may be helpful in symmetry-related or other atypical obsessions. Electroconvulsive therapy (ECT) should be reserved for severely depressed and suicidal OCD patients. Neurosurgery is the last resort current operations include anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leucotomy. The outcome of such operations is questionable. 

No pharmacokinetic interaction occurs between imipramine or mirtazapine and olanzapine, but the additive effects of clomipramine and olanzapine was thought to have caused a seizure in one patient. 

Noninterfering amitriptyline, bupropion, citalopram, clomipramine, clozapine, dox-epin, haloperidol, 2-hydroxydesipramine, 2-hydroxyimipramine, imipramine, loxapine, moclobemide, olanzapine, risperidone... 

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