Combination therapy for cognitive distortions, resisting relapse of unipolar non-psychotic depression

Abstract

The present invention relates to a new method of treatment for persons meeting diagnoses for major depressive disorder, or other unipolar (non-bipolar, non-psychotic and non-treatment resistant) depression. The method comprises administering a combination of two categories of drugs, antipsychotics or dopamine system stabilizers, in combination with a newer antidepressant such as a selective serotonin reuptake inhibitor, as initial treatment or as soon as possible. The method targets the prevention of suicide, and provides other benefits including preventing disease progression development of tolerance toward the antidepressants. Another aspect of the invention relates to using the method for alleviating cognitive distortion and related functional impairment or health risks, and/or using the method for smoking cessation or nicotine withdrawal.

1 . A method for treatment of a non-psychotic patient having cognitive distortions with functional impairment or health hazards, wherein said method comprising administering to said patient an effective amount of an antidepressant, wherein said antidepressant is selected from the group consisting of serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, combined action SSRI/SNRI, serotonin-2 antagonist/reuptake inhibitors, an antidepressant with alpha-2 antagonism plus serotonin-2 and serotonin-3 antagonism, an antidepressant with serotonin/norepinephrine/dopamine reuptake inhibition, an antidepressant with norepinephrine and dopamine reuptake inhibition, 5-HT-1alpha antagonist, 5-HT-1beta antagonist, 5-HT1A receptor agonists, 5-HT1A receptor agonists and antagonists, 5-HT2 receptor antagonists, viloxazine hydrochloride, dehydroepiandosterone, NMDA receptor antagonists, AMPA receptor potentiators, substance P antagonists/neurokinin-1 receptor antagonists, nonpeptide Substance P antagonist, neurokinin 2 antagonists, neurokinin 3 antagonists, corticotropin-releasing factor receptor antagonists, antiglucocorticoid medications, glucocorticoid receptor antagonists, cortisol blocking agents, nitric oxide synthesize inhibitors, inhibitors of phosphodiesterase, enkephalinase inhibitors, GABA-A receptor agonists, free radical trapping agents, atypical MAOI's, selective MAOI inhibitors, hormones, folinic acid, leucovorin, tramadol, and tryptophan in combination with an antipsychotic drug, and wherein said antipsychotic drug is selected from the group consisting of an atypical antipsychotic drug, and a dopamine system stabilizer. 
     
     
         2 . The method of  claim 1 , wherein said antipsychotic drug is an atypical antipsychotic. 
     
     
         3 . The method of  claim 2 , wherein said atypical antipsychotic drug is selected from the group consisting of quetiapine, risperidone, ziprasidone, olanzapine, iloperidone, melperone, amperozide, and pharmaceutically acceptable salts thereof. 
     
     
         4 . The method of  claim 1 , wherein said antidepressant is selected from the group consisting of fluoxetine, norfluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram, bupropion, nefazodone, mirtazapine, venlafaxine, duloxetine, milnacipran, reboxetine, zimelidine, indalpine, gepirone, femoxetine, alaproclate, clomipramine and pharmaceutically acceptable salts thereof, and wherein said atypical antipsychotic drug is selected from the group consisting of risperidone, quetiapene, olanzapine, ziprasidone and aripiprazole. 
     
     
         5 . The method of  claim 1 , wherein said antidepressant is selected from the group consisting of serotonin reuptake inhibitors, a selective norepinephrine reuptake inhibitors, combined action SSRI/SNRI, serotonin-2 antagonist/reuptake inhibitors, an antidepressant with alpha-2 antagonism plus serotonin-2 and serotonin-3 antagonism, an antidepressant with serotonin/norepinephrine/dopamine reuptake inhibition and an antidepressant with norepinephrine and dopamine reuptake inhibition. 
     
     
         6 . The method of  claim 1 , wherein said antidepressant is selected from the group consisting of 5-HT-1alpha antagonist, 5-HT-1beta antagonist, 5-HT1A receptor agonists, 5-HT1A receptor agonists and antagonists, 5-HT2 receptor antagonists, viloxazine hydrochloride, dehydroepiandosterone, NMDA receptor antagonists, AMPA receptor potentiators, substance P antagonists/neurokinin-1 receptor antagonists, nonpeptide Substance P antagonist, neurokinin 2 antagonists, neurokinin 3 antagonists, corticotropin-releasing factor receptor antagonists, antiglucocorticoid medications, glucocorticoid receptor antagonists, cortisol blocking agents, nitric oxide synthesize inhibitors, inhibitors of phosphodiesterase, enkephalinase inhibitors, GABA-A receptor agonists, free radical trapping agents, atypical MAOI's, selective MAOI inhibitors, hormones, folinic acid, leucovorin, tramadol, and tryptophan. 
     
     
         7 . The method of  claims 1 , wherein said antidepressant is a selective serotonin reuptake inhibitor. 
     
     
         8 . The method of  claim 4 , wherein said antipsychotic is selected from the group consisting of risperidone, quetiapene, olanzapine, ziprasidone and aripiprazole, and the effective amount per day is from 0.5 mg to 4 mg for risperidone, from 25 mg to 400 mg for quetiapine, from 2.5 mg to 10 mg for olanzapine, from 10 mg to 40 mg for ziprasidone, and 2.5 mg to 15 mg for aripiprazole. 
     
     
         9 . The method of  claims 4 , wherein an effective amount of said antidepressant is its recommended therapeutic dose, or its effective starting dose. 
     
     
         10 . The method of  claims 1 , wherein the administration is oral. 
     
     
         11 . The method of  claim 1  wherein said cognitive distortions are in non-psychotic unipolar depression and wherein said treatment is effected for at least one of the group consisting of delaying relapse of said non-psychotic unipolar depression; resisting relapse of said non-psychotic unipolar depression; and resisting the recurrence of said non-psychotic unipolar depression. 
     
     
         12 . The method of  claim 5  wherein said cognitive distortions are in non-psychotic unipolar depression and wherein said treatment is effected for at least one of the group consisting of delaying relapse of said non-psychotic unipolar depression; resisting relapse of said non-psychotic unipolar depression; and resisting the recurrence of said non-psychotic unipolar depression. 
     
     
         13 . The method of  claim 6  wherein said cognitive distortions are in non-psychotic unipolar depression and wherein said treatment is effected for at least one of the group consisting of delaying relapse of said non-psychotic unipolar depression; resisting relapse of said non-psychotic unipolar depression; and resisting the recurrence of said non-psychotic unipolar depression. 
     
     
         14 . The method of  claim 1 , wherein said cognitive distortions are in non-psychotic unipolar depression and said treatment is effected for at least one of the group consisting of protecting against the development of tolerance toward the antidepressant; and remedying the development of tolerance toward said antidepressant. 
     
     
         15 . The method of  claim 1  wherein said cognitive distortions are in non-psychotic unipolar depression and wherein said treatment is effected for at least one of the group consisting of avoiding a paradoxical effect of said antidepressant sensitizing said patients to said unipolar depression; treating a paradoxical effect of said antidepressant sensitizing said patients to said unipolar depression; for avoiding worsening of said unipolar depression from said antidepressant; and treating worsening of said unipolar depression from said antidepressant. 
     
     
         16 . The method of  claim 5  wherein said cognitive distortions are in non-psychotic unipolar depression and wherein said treatment is effected for at least one of the group consisting of avoiding a paradoxical effect of said antidepressant sensitizing said patients to said unipolar depression; treating a paradoxical effect of said antidepressant sensitizing said patients to said unipolar depression; for avoiding worsening of said unipolar depression from said antidepressant; and treating worsening of said unipolar depression from said antidepressant. 
     
     
         17 . The method of  claim 6  wherein said cognitive distortions are in non-psychotic unipolar depression and wherein said treatment is effected for at least one of the group consisting of avoiding a paradoxical effect of said antidepressant sensitizing said patients to said unipolar depression; treating a paradoxical effect of said antidepressant sensitizing said patients to said unipolar depression; for avoiding worsening of said unipolar depression from said antidepressant; and treating worsening of said unipolar depression from said antidepressant. 
     
     
         18 . The method of  claim 1 , wherein said cognitive distortions are in non-psychotic unipolar depression and wherein said treatment is given for treating residual symptoms of said unipolar depression. 
     
     
         19 . The method of  claim 1 , wherein said antidepressant is selected from the group consisting of serotonin reuptake inhibitors, a selective norepinephrine reuptake inhibitors, combined action SSRI/SNRI, serotonin-2 antagonist/reuptake inhibitors, an antidepressant with alpha-2 antagonism plus serotonin-2 and serotonin-3 antagonism, an antidepressant with serotonin/norepinephrine/dopamine reuptake inhibition and an antidepressant with norepinephrine and dopamine reuptake inhibition, and wherein said antipsychotic drug is an atypical antipsychotic. 
     
     
         20 . The method of  claim 5  wherein said cognitive distortions are in non-psychotic unipolar depression and wherein said treatment is effected for at least one of the group consisting of delaying relapse of said non-psychotic unipolar depression; resisting relapse of said non-psychotic unipolar depression; and resisting the recurrence of said non-psychotic unipolar depression, and wherein said antipsychotic drug is an atypical antipsychotic.