Academic journal article Hong Kong Journal of Psychiatry

Management of Treatment-Resistant Depression in the Late 1990s

Academic journal article Hong Kong Journal of Psychiatry

Management of Treatment-Resistant Depression in the Late 1990s

Article excerpt


Although most depression responds well to ether antidepressant medications or psychological therapies, for a significant proportion of patients this condition is either chronic or frequently recurrent. This article outlines an approach to assessing both somatic and psychasocial contributants to selective serotonin re-uptake inhibitor (SSRI) resistant depression, and then reviews the various somatic therapies which have been described for this. The major treatment approaches are: increasing dosage, augmenting or combination of antidepressants; changing to a different antidepressant, or electroconvulsive therapy. The current research evidence for each of these treatment options is critically reviewed.

Key words: depression, treatment-resistant, antidepressants, augmentation


Inadequate response to antidepressants is not uncommon. The U.S. Collaborative Study on the Psychobiology of Depression--one of the major follow-up studies of depressed patients--has demonstrated significant rates of both chronicity and recurrence. In early reports from that study, Keller et al. (1984) found that 21% of patients had not recovered after two years. After five years, 12% still remained depressed (Keller et al., 1992). Longer follow-up studies over 15 to 20 years by other groups (e.g. Kiloh et al., 1988; Lee and Murray, 1988) have found similarly High rates of both chronic and recurrent depression.

Although the term "treatment-resistant depression" is used commonly, there is little agreement over how such a term should be defined (Wilhelm et al., 1994). Fawcett and Kravitz (1985), for example, have described seven levels of treatment resistance, with each level being defined is terms of duration of illness, as well as type and dose of particular somatic therapies.

This article will be based upon the premise that there are different severities of treatment-resistance, which vary from non-response to a single adequate cause of an antidepressant to failure to benefit from a number of antidepressant therapies including ECT. Furthermore, it will arbitrarily define the "benchmark" level of treatment resistance as failure to respond to an adequate course of SSRI medications. Such a pragmatic definition will be used as SSRIs have now become the first-line antidepressant therapy in bath general and psychiatric practice in many countries.

Which patients are likely to be refractory to antidepressant medications? Recently, Nelson et al. (1994) found that patients who failed to respond to the tricyclic desipramine were more likely to have a personality disorder, prior treatment failure, "near delusional" status, and be less than 35 years of age. Other less significant characteristics of non-responders were longer duration of the current episode, recurrent depression, dysthymia and secondary depression. Bonner and Howard (1995), studying an elderly population, found resistance to be associated with onset of depression before 50, hypochondriacal features and the presence of cognitive impairment.

The most effective means of treating depression incorporate both biological and psychological therapies (Wilhelm et al., 1994; Mitchell, 1997a). There has been a tendency, however, far psychological therapies to be undervalued in the treatment of depressed patients, particularly those with a non-melancholic subtype. While this article will focus upon the rote of physical therapies, this should not be interpreted as minimising the importance of non-pharmacological options.

Prior to detailing specific therapies for treatment-resistant depression, it is necessary to comment upon the consequences of such failure to respond. For those suffering from treatment-resistant depression there is severe demoralisation, as the hopes and expectations of recovery with each succeeding course of antidepressants are repeatedly dashed. Low salt-esteem and self-confidence lead to a gradual but inevitable withdrawal from family, friends and previous interests. …

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