Depression combination therapy

Psychotically depressed individuals generally require either ECT or combination therapy with an antidepressant and an antipsychotic agent. 

Tablet combination therapy Adverse reactions occurring in at least 3% of patients include the following Abdominal pain alopecia anemia anorexia anxiety arthralgia back pain bacterial infection blurred vision concentration impairment cough depression dermatitis diarrhea dizziness dry mouth/skin dyspepsia dyspnea eczema fatigue/asthenia headache hypothyroidism increased sweating injection site reaction insomnia irhtability/anxiety/nervousness lymphopenia memory impairment mood alteration myalgia nausea neutropenia pain pruritus pyrexia rash resistance mechanism disorders rigors thrombocytopenia vomiting weight decrease.

A 32-year-old Haitian man has acute-onset confusion and suicidal ideation. Two weeks ago he began combination therapy for multi-drug resistant pulmonary tuberculosis. He has a history of depression that required intermittent treatment in the past. Which of the following antitubercular agents is responsible for the patient s neurological symptoms ... 

To date, only one study has been completed with an antidepressant other than a TCA combined with an antipsychotic in the treatment of PMD. Rothschild and colleagues (1993) investigated the efficacy of fluoxetine and perphenazine in the treatment of PMD and found that approximately 73% of 30 patients who met DSM-III-R (American Psychiatric Association 1987) criteria for major depression with psychotic features had at least a 50% reduction on their Hamilton Rating Scale for Depression scores over 5 weeks. Furthermore, the combination of fluoxetine and perphenazine appeared to be better tolerated than the combination of TCAs with antipsychotics. Although there is no evidence that monotherapy with an antidepressant other than amoxapine is efficacious, the combination therapy with many antidepressants other than the TCAs may prove useful. 

Bakish D, Hooper CL, Filteau MJ, et al A double-blind placebo-controlled trial comparing fluvoxamine and imipramine in the treatment of panic disorder with or without agoraphobia. Psychopharmacol Bull 32 135-141, 1996 Bakish D, Hooper CL, Thorton MD, et al Fast onset an open study of the treatment of major depressive disorder with nefazodone and pindolol combination therapy. Int Clin Psychopharmacol 12 91-97, 1997 Baldwin DS Depression and sexual function. J Psychopharmacol 10 (suppl l) 30-34, 1996... 

Lithium, lamotrigine, and olanzapine-fluoxetine combination therapy are first-line treatments for bipolar depression. The response... 

Fatenri, S.H., Emamian, E.S., Kist, D. Venlafaxine and bupropion combination therapy in a case of treatment-resistant depression. Ann. Phannacother. 33, 701—703, 1999. 

Certain disorders may require combined therapy. For example, SA-bipolar type may best respond to the addition of mood stabilizers, and BZDs may be useful adjuncts for agitated psychoses. Conversely, some mood disorders may require augmentation with antipsychotics (e.g., delusional depression). Unfortunately, except for schizophrenia, most other psychotic conditions have not been systematically studied to determine the optimal use of these agents. 

FIGURE 7-36. This figure summarizes both first-line monotherapies and the most commonly used combination therapies for unipolar depression. Note that antidepressant combinations at the far right and the end of the line are to be used after other strategies fail. 

Flutamide (EULEXIN, EUFLEX) Nonsteroidal LH increased T increased Monotherapy Combination therapy Potency spared Breast tenderness, nausea and vomiting, diarrhea, rectal bleeding, hot flashes, cystitis, increased appetite, sleep disturbances, hepatotoxicity, anemias, hemolysis, headache, dizziness, malaise, blurred vision, anxiety, depression, decreased libido, hypertension, complications in patients with cardiovascular disease... 

A double-blind study in which 31 patients with breakthrough depression taking lithium received augmentation with either paroxetine or amitriptyline and showed a quantitative increase in tremor activity with combined therapy, but no significant change in tremor frequency (214). 

The adverse effects of lithium in elderly patients include cognitive status worsening, tremor, and hypothyroidism. The authors suggested that divalproex is also useful in elderly patients with mania and that concentrations of divalproex in the elderly are similar to those useful for the treatment of mania in younger patients. They noted that carbamazepine should be considered a second-line treatment for mania in the elderly. A partial response would warrant the addition of an atypical antipsychotic drug. For bipolar depression, they recommended lithium in combination with an antidepressant, such as an SSRI. They also noted that lamotrigine may be useful for bipolar depression. Electroconvulsive therapy (ECT) may also be useful, but there have been no comparisons of ECT and pharmacotherapy in elderly patients with bipolar depression. 

Taking depression as an example, an extensive evidence base exists for the efficacy of several forms of psychotherapy. These include cognitive therapy (in which individuals identify faulty views and negative automatic thoughts and attempt to replace them with ways of thinking less likely to lead to depression), interpersonal therapy (which focuses on relationships, roles and losses), brief dynamic psychotherapy (a time-limited version of traditional psychoanalysis) and cognitive analytical therapy (another well structured time-limited therapy which combines the best points of cognihve therapy and traditional analysis). 

Dosage An initial dose of azathioprine of 1—2 mg/kg BW/day (rounded off to the nearest 25 mg or 50 mg tablet) is recommended. A maintenance dose of 50-75 (—100) mg/day is sufficient. We always administered the combination therapy from the outset and thereby did not observe any side effects from azathioprine — minor fluctuations in bone-marrow depression reverted to normal values spontaneously or after a short period of reduced dosage (25 mg). With this maintenance dose, we retained a... 

The FDA has expanded the indications for a combination product to include patients with chronic hepatitis C who have not been treated with interferon alfa. This product, Rebetron Combination Therapy (Schering), contains recombinant interferon alfa-2b for injection (Intron A) plus ribavirin (Rebetol) in capsules, and was previously only approved for patients who had relapsed after treatment with interferon alone (401). Serious adverse effects, such as depression, suicidal ideation, and suicide, have occurred with this regimen and patients should be closely monitored. 

Combination therapies may be needed for the treatment of acute mania or mixed episodes, breakthrough depression, and rapid cycling Reassessment of combination and adjunctive therapies should be done routinely and unnecessary medications should be tapered off gradually and discontinued... 

Inereased sedative and respiratory depressant effeets are to be expeeted when benzodiazepines are used with opioids. The manufaeturers of sufentanil and alfentanil suggest that elinieally important hypotension may oeeur and this may be exaeerbated by the use of benzodiazepines it would seem prudent to be alert for this. The manufaeturers of transdermal fentanyl also warn of the possibility of respiratory depression, hypotension, profound sedation and potentially coma with concurrent CNS depressants including benzodiazepines. When such combined therapy is contemplated, the dose of one or both drugs should be significantly reduced. ... 

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