Antidepressants combination therapy with

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

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. 

The role of lamotrigine in the treatment of bipolar disorder has been reviewed, and combination therapy with lamotrigine plus other mood stabilizers, including lithium, has been particularly discussed (81). Lamotrigine has a favorable tolerability profile compared with lithium, but lithium has better antimanic effects than lamotrigine, which exerts its antidepressant effects sooner than lithium. 

Viewed as a whole, this investigation supports the view that tricyclic antidepressants are particularly effective in cases of endogenous depression, whereas psychotherapy, possibly in conjunction with drug therapy, constitutes the best solution in cases of situative depression (which would probably be termed reactive depression in the terminology used hitherto). It is interesting to note that the combination of drug therapy with psychotherapy provided additional benefit in patients with endogenous depression. It must, however, be stated that this final conclusion is only based on a fairly small subsample. 

Treatment Implications. A review of response rates found that only 35% of patients with psychotic depression responded to treatment with a tricyclic antidepressant alone versus 67% of patients with nonpsychotic depression (Table 6-6) (13). Yet these patients have a better response to electroconvulsive therapy (ECT) (14). These patients have also been found to respond to combined treatment with an antidepresssant and an antipsychotic in comparison with either an antidepressant or antipsychotic alone (15). Despite these data, one study found that less than 50% of patients with psychotic depression referred to an ECT service had been treated with an antipsychotic and only 15% had received a daily dose equivalent to 200 mg or more or chlorpromazine ( 16). 

A study in 17 lithium-maintained patients found that tremor increased significantly when amitriptyline 75 to 150 mg daily was added. The greatest increments occurred within approximately 3 weeks of starting the combined treatment, but tremor activity was still significantly greater than baseline after 6 weeks. No patient discontinued treatment because of the increase in tremor. Seizures occurred in a patient on amitriptyline 300 mg daily, 13 days after lithium carbonate 300 mg three times daily was started. After recovery, combined therapy was resumed, but further seizures occurred 10 days later. Her lithium levels were 0.9 mmol/L three days before this second episode. She later took amitriptyline 500 mg daily without adverse effect. Another patient developed neuroleptie malignant syndrome after one week of treatment with lithium carbonate 300 mg and amitriptyline 25 mg, both three times daily. The patient had also received chlorpromazine for one week, just before the lithium-antidepressant therapy was started. No pharmacokinetic interaction was found in 10 therapy-resistant patients with major depression who were given amitriptyline and lithium for 4 weeks. ... 

Two separate reports have suggested that supraphysiological doses of liothyronine may be beneficial in refractory major depression when combined with both tricyclic antidepressants and SSRIs [8, 9 ]. Preliminary evidence suggests that the presence of a functional polymorphism in the type 1 de-iodinase enzyme, resulting in reduced peripheral conversion of T4 to T3, may be associated with increased benefit from combination therapy of antidepressants with liothyronine [10 ]. 

The authors concluded that antidepressants exert a modest beneficial effect for patients with combined depressive disorder and substance use disorder. They also emphasized that antidepressants are not a stand-alone treatment for depressed alcoholic patients and that concurrent therapy directly targeting the substance use disorder is also indicated. 

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

Lamotrigine is effective for the maintenance treatment of bipolar I disorder in adults. It has both antidepressant and mood-stabilizing effects, and it may have augmenting properties when combined with lithium or valproate. It has low rates of switching patients to mania. Although it is less effective for acute mania compared to lithium and valproate, it may be beneficial for the maintenance therapy of treatment-resistant bipolar I and II disorders, rapidcycling, and mixed states. It is often used for bipolar II patients. 

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