Moderate depression

Glass lA Antiarrhythmic Agents. Class lA antiarrhythmic agents decrease automaticity, ie, depress pacemaker rates, especially ectopic foci rates produce moderate depression of phase 0 depolarization and thus slow conduction in atria, A-V node, His-Purkinje system, and ventricles prolong repolarization, ie, lengthen action potential duration increase refractoriness and depress excitabiHty. These electrophysiological effects are manifested in the ECG by increases in the PR, QRS, and QT intervals. 

Scoring 0-4 = None or minimal depression 5-7 = Mild depression 8-15 = Moderate depression 16+ = Severe depression... 

Various forms of psychotherapy are regarded as effective interventions in mild to moderate depression, but studies comparing the economics of psychotherapy and pharmacotherapy are few (Rosenbaum and Hylan, 1999). One study found that the total health-care costs for patients who received psychotherapy were no different from those for patients who received an antidepressant. However, no efficacy measure was used (Edgell and Hylan, 1997). A randomized, prospective study which evaluated the treatment of depression with nortriptyline, interpersonal therapy or treatment as usual, with outcomes expressed in quality-adjusted life years, found that nortriptyline but not interpersonal therapy was a cost-effective alternative to treatment as usual (Lave et al, 1998). 

Schrader, E. (2000). Equivalence of St John s Wort extract (Ze 117) and fluoxetine a randomized, controlled study in mild-moderate depression. Int. Clin. Psychopharmacol., 15, 61-8. 

Compared to antipsychotics, there are even fewer studies on the prescribing patterns of antidepressants done in Asian countries. Pi etal. (1985) conducted a survey of psychotropic prescribing practices reported by psychiatrists in 29 medical schools in 9 Asian countries. Daily dose range of tricyclic antidepressants (TCAs) such as amitriptyline, imipramine, and nortriptyline in Asian countries was comparable to the practice in USA. This is despite differences found between Asian and non-Asian populations in the pharmacokinetics of TCAs (Pi et al, 1993). A questionnaire on the practical prescribing approaches in mood disorders administered to 298 Japanese psychiatrists was reported by Oshima et al. (1999). As first-line treatment, the majority of respondents chose newer TCAs or non-TCAs for moderate depression and older TCAs for severe depression. Combination of antidepressants and anxiolytics was preferred in moderate depression, while an antidepressant and antipsychotic combination was common in severe psychotic depression. Surprisingly, sulpiride was the most favored drug for dysthymia. In a naturalistic, prospective follow-up of 95 patients with major depression in Japan, the proportion of patients receiving 125 mg/day or less of imipramine was 69% at one month and 67% at six months (Furukawa et al., 2000). 

Psychotherapy looks even better when its long-term effectiveness is assessed.17 Formerly depressed patients are far more likely to relapse and become depressed again after treatment with antidepressants than they are after psychotherapy. As a result, psychotherapy is significantly more effective than medication when measured some time after treatment has ended, and the more time that has passed since the end of treatment, the larger the difference between drugs and psychotherapy. This long-term advantage of psychotherapy over medication is independent of the severity of the depression. Psychotherapy outperforms antidepressants for severely depressed patients as much as it does for those who are mildly or moderately depressed.18... 

Philipp, Michael, Ralf Kohnen and Karl O. Hiller, Hypericum Extract Versus Imipramine or Placebo in Patients with Moderate Depression Randomised Multicentre Study ofTreatment for Eight Weeks , British Medical Journal 319 (1999) 1534-39... 

Optimize the dose of mood stabilizing medication(s) before adding on lithium, lamotrigine, or antidepressant (e.g, bupropion or an SSRI) if psychotic features are present, add on an antipsychotic ECT used for severe or treatment-resistant depressive episodes or for psychosis or catatonia Mild to Moderate Depressive Episode Severe Depressive Episode... 

St. John s wort, an herbal nonprescription medication containing hyperi-cum, may be effective for mild to moderate depression, but it is associated with several drug-drug interactions. Its potency, purity, and manufacture are not regulated by the FDA. As depression is a potentially life-threatening disease, all antidepressant treatments should be overseen by a trained healthcare professional. 

The values of Cbr for each geographical area were ranged to determine the type of biogeochemical cycling and these ranks are shown in Table 3. Five types of biogeochemical cycling are divided very intensive, intensive, moderate, depressive and very depressive. 

Laakmann G, Schule C, Baghai T, Kieser M. (1998). St. John s wort in mild to moderate depression the relevance of hyperforin for the clinical efficacy. Pharmacopsychiatry. 31(suppl 1) 54-59. 

In animal studies, effects of exposure include increased mortality gonadal atrophy, and carcinomas. The LCso for rats was 3 68 ppm for 1 hour and 103 ppm for 8 hours. Irritation of the eyes and respiratory tract was observed at levels of 60 ppm and higher. Moderate depression of the central nervous system was manifested as sluggishness and ataxia. 

The efficacy of fluoxetine in treating patients with moderate depression is comparable to the efficacy of tricyclic antidepressants. It is capable of elevating mood and removing feelings of fear and stress. It does not have a sedative effect. Fluoxetine is used in depression as well as in bulemic neuroses. Use of fluoxetine is preferred in cases when sedative, hypotensive, and anticholinergic side effects caused by other antidepressants are con-traindicative to patients. Prozac is a synonym for fluoxetine. 

Methylphenidate is a CNS stimulant similar to amphetamine however, in usual doses it has a more expressed action on mental activity rather than physical or motor activity. In therapeutic doses it does not raise blood pressure, respiratory rate, or increase heart rate. All of these effects as well as a number of others are associated with general excitement of the CNS. Tremor, tachycardia, hyperpyrexia, and a state of confusion can result from using large doses. It is used in treating moderate depression and apathetic conditions, and also as an adjuvant drug for treating attention deficit disorder in children.Synonyms of this dmg are meridil, ritalin, and others. 

Mild to moderate depression An initial dose of 75 mg/day is suggested for outpatients. In some patients, especially the elderly, an initial dose of 25 mg/day may be used. Because of the long half-life of maprotiline, maintain initial dosage for 2 weeks. Gradually increase the dosage in 25 mg increments, as required and tolerated. Most patients respond to a dose of 150 mg/day, but doses as high as 225 mg/day may be required. 

St. John s wort is very popular as a physician-prescribed antidepressant in Europe and is widely used for this purpose—usually without medical guidance—in the United States. A meta-analysis of 23 studies concluded that St. John s wort was more effective than placebo in treating mild to moderate depression and was as effective as imipramine and standard antidepressants. It was also better tolerated than the antidepressants to which it was compared. A recent meta-analysis, however, failed to find St. John s wort effective for severe depression. 

A multicenter trial comparing more appropriate doses of imipramine (75 mg twice daily, N = 167) and St. John s wort extract (250 mg twice daily standardized to 0.2% hypericin, N = 157) showed no difference in efficacy after 6 weeks of treatment. However, St. John s wort seemed to reduce anxiety symptoms more often than imipramine and was better tolerated (Woelk, 2000). A study including 240 participants compared St. John s wort with fluoxetine in mild to moderate depression and also concluded that efficacy of both treatments was comparable (Schrader, 2000). These results have been replicated in a smaller trial us-... 

There is no empirical evidence available for clinical use in children and adolescents. Yet, Hypericum seems to be used for the treatment of mild to moderate depression in the young (Walter et ah, 2000). St. John s wort should be avoided in young patients with severe depression and bipolar disorder (given the lack of adult data about effectiveness and risk of manic induction, respectively) and in those who have significant suicide risk. Treatments of proven efficacy (e.g., SSRIs, mood stabilisers) should be preferred in these cases. However, St. John s wort may be considered in cases of unipolar depression where conventional treatments have failed and prior to the use of combinations of drugs that have an increased risk of side effects and whose efficacy has not been demonstrated. 

For women who are planning to become pregnant and who have had mild to moderate depression, a trial of medication taper and discontinuation is appropriate. Plans for relapse should be discussed prior to the trial. This strategy may not be appropriate for women who have had severe or multiple episodes of depression, as a recent study reported that pregnant women with a history of recurrent depression were at significant risk for relapse when medication was discontinued (Cohen et ah, 1997). 

In a similar, but larger, double-blind study, 107 patients with unipolar and bipolar depression and 25 patients with PMD were randomly selected to either amitriptyline or imipramine after a 2-week placebo washout [Kocsis et al. 1990]. Doses of both drugs averaged >200 mg/day for 4 weeks. Approximately 67% of the moderately depressed patients with NPMD responded to pharmacotherapy, whereas only 32% of the patients with PMD experienced significant improvement with either drug. However, when severely depressed patients with NPMD [with Hamilton Rating Scale for Depression scores of >27] were compared with the patients with PMD, no difference in response rate was noted. 

Complement psychotherapies (cognitive and interpersonal) in mild to moderate depressive episodes... 

Despite the diagnostic challenges that remain in trying to understand the nature of MDD in children and adolescents, advances in its treatment has progressed considerably since the last edition of this textbook. Over this interval, selective serotonin reuptake inhibitors (SSRIs) have superseded TCAs as the treatment of first choice based both on efficacy and safety considerations. As in adults, specific psychotherapies (cognitive therapy, cognitive-behavioral therapy, and interpersonal therapy) may be as effective as antidepressant medication, at least in mild to moderate depression in children and adolescents ( 111, 112). Also, evidence indicates that depression in children and adolescents may be more influenced than is depression in adults by psychosocial variables such as peers and family, as well as other environmental factors (113). 

The adverse effects of TCAs are also similar to those reported in adults (see Chapter 7). The secondary amine TCAs (e.g., desipramine, nortriptyline) are generally as well tolerated as newer antidepressants. Increased blood pressure may be more likely to occur in children than in adults but hypertension per se is rare ( 135). The most common cardiovascular effect is mild tachycardia. Despite their generally favorable adverse effect profile, secondary amine TCAs can cause serious toxicity in children and adolescents just as in adults when a taken in an overdose or when a high TCA plasma level occurs as a result of slow metabolism ( 136). For that reason, most clinicians reserve TCAs for the child or adolescent who has at least a moderate depressive disorder unresponsive to a trial of one or more newer antidepressants. In such instances, TDM should be done at least once to ensure plasma concentrations greater than 450 ng/mL do not develop ( 137). Such levels are associated with an increased risk of the following ... 

St. John s wort (Hypericum perforatum) is a perennial wildflower indigenous to Europe, North Africa, and western Asia (Fig. 1) and has been used for medicinal purposes for over two millennia. As far back as the early 16th century, St. John s wort was used primarily to treat anxiety, depression, and sleep disorders. In the late 20th and early 21st century, St. John s wort has been recommended for the treatment of mild to moderate depression (7). In support of its use for the treatment of mild to moderate depression, a number of clinical trials have demonstrated that St. John s wort has comparable efficacy to the tricyclic antidepressants (i.e., imipramine) and selective serotonin reuptake inhibitors (e.g., fluoxetine and paroxetine) (8-13). 

Behnke K, Jensen GS, Graubaum HJ, Gruenwald J. Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression. Adv Ther 2002 19(l) 43-52. 

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