TREATMENT OF PARTIALLY RESPONSIVE AND NONRESPONSIVE PATIENTS

There is little benefit in making treatment changes before three weeks, other than to mitigate side effects. Changes in treatment strategy should be considered after the physician is satisfied that the patient has been treated with an adequate dosage of the antidepressant for an adequate time, with current medications increased to the limit of side effect tolerance.

In patients showing an inadequate response after a reason- able time, the decision is either to continue with the same medication and augment with an additional agent, or to switch medications altogether, depending on whether the patient has shown any response to the current strategy. Partial responders may be more likely to benefit from treatment augmentations, whereas patients who show no response or worsen during treatment warrant a new agent.

Antidepressant Augmentation Typical augmentation strategies shown in Table 2-4 include the

addition of lithium carbonate, thyroid hormone, a stimulant,

64 HANDBOOK OF PSYCHIATRIC DRUGS

an atypical antipsychotic, or by the use of antidepressant combinations.

LITHIUM AUGMENTATION Lithium has been used successfully with most antidepressants, including TCAs, serotonin reuptake inhibitors, and bupropion, with response rates as high as 65%. The blood level of lithium necessary for adjunctive use has not been well established. It is probably best to start at a low dose (300 mg b.i.d) and increase to a therapeutic blood level (0.8 to 1.2 mEq/L) if there is no response. It may take three to six weeks for augmenting effect.

If augmentation is successful, it should be continued throughout the acute phase of treatment. This strategy can be limited by side effects and lithium’s narrow therapeutic index. It is associated with hypothyroidism, tremor, increased thirst, increased urination, nausea, weight gain, and acne. Patients should be cautioned to avoid dehydration, which can precipi- tate toxic lithium blood levels.

THYROID HORMONE AUGMENTATION

The trial should continue for at least three weeks. Reported response rates for thyroid augmentation are lower than those for lithium augmentation (25%). As with lithium augmentation, if there is a positive response, it occurs relatively early.

STIMULANT AUGMENTATION Methylphenidate and dextroamphetamine at dosages between

5 and 20 mg have been used for antidepressant augmentation, but there are few systematic data regarding the proper dose or length of treatment for this potential use.

ANTIDEPRESSANT DRUG AUGMENTATION Second-generation antipsychotic drugs are increasingly being used adjunctively with antidepressants for residual or treatment-resistant symptoms. APDs are generally used within their therapeutic range.

Augmentation Strategies

LENGTH OF

REPORTED

AGENT

COMMENTS Lithium carbonate

DOSING STRATEGY

TRIAL

RESPONSE RATE

Start at 300 mg b.i.d., increase

3–6 wks

As high as 65%

Best documented strategy; has been

to therapeutic blood level

combined with most agents

(0.8–1.2 mEq/L)

Triiodothyronine

Equal to lithium in one placebo controlled trial Stimulants

At least 3 wks

At 25%

Few systematic data (methylphenidate dextroamphetamine)

Atypical antipsychotics Begin with low dose (e.g.,

Mainly open trials; controlled studies

olanzapine 2.5 mg/day,

in progress

aripiprazole 5 mg/day) gradually increase to full therapeutic dose if needed

Combined May need lower doses than

Mainly open trials; controlled studies antidepressant

in progress therapy

usual (due to enzyme

inhibition) †

Psychotherapy N/A

Varies by

Good data for both

therapy

cognitive–behavioral therapy and interpersonal therapy

† Inadequate data.

66 HANDBOOK OF PSYCHIATRIC DRUGS COMBINED ANTIDEPRESSANT THERAPY

Open trials have supported the use of combined therapy of

a TCA and a serotonin reuptake inhibitor in patients for whom either class alone has failed. When antidepressants are combined, it is important to remember that the serotonin reuptake inhibitors can potentiate TCA levels, and this should be monitored carefully. MAOIs have also been used in combi- nation with TCAs, although this should be monitored closely given the risk of potential toxic interactions. Given the risk of

a serotonin syndrome, MAOIs should not be combined with serotonin reuptake inhibitors. Bupropion is frequently added to an SSRI to enhance efficacy or to alleviate side effects such as decreased libido, fatigue, and sedation.

NONPHARMACOLOGICAL APPROACHES

A number of nonpharmacological augmentation options exist, particularly the concomitant use of psychotherapy. The combi- nation of psychotherapy and medication may offer benefits that either therapy alone cannot offer, including additional efficacy as well as prevention of relapse. This has been shown to some degree for both cognitive–behavioral therapy and interpersonal therapy.

TREATMENT OF PARTIALLY RESPONSIVE AND NONRESPONSIVE PATIENTS