Cancer Health Center

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Atypical antidepressants (e.g., mirtazapine) are sometimes used to treat anxiety disorders because of their added effects on comorbid symptoms such as insomnia. Older medications such as tricyclic antidepressants (e.g., imipramine and clomipramine) and monoamine oxidase inhibitors (e.g., phenelzine) are also effective in treating anxiety disorders. The use of antidepressants in clinical practice is limited by their unfavorable side effects, poorer tolerability, and higher risks of toxicity.[26]

(Refer to Table 2 in the PDQ summary on Depression for antidepressant dosing. Refer to the Suicide Risk in Cancer Patients section in the PDQ summary on Depression for risk of suicidality and other neuropsychiatric side effects.)

Buspirone, a nonbenzodiazepine, is useful in patients who have not previously been treated with a benzodiazepine and in those who may abuse benzodiazepines (e.g., those with a history of illicit substance abuse or alcoholism). Buspirone is also useful in the geriatric population to augment fluoxetine for the treatment of anxiety and depression. The beginning dose is 5 mg 3 times a day and can be increased to 15 mg 3 times a day. Buspirone can also be given twice a day.

The use of specific classes of medications is considered for managing treatment-refractory anxiety symptoms or in certain special clinical situations. Low-dose neuroleptics (e.g., thioridazine, 10 mg 3 times a day; and risperidone, 1 mg twice a day) are used to treat severe anxiety when an adequate dose of a benzodiazepine is ineffective or if the patient might be expected to respond poorly to benzodiazepines (e.g., patients with brain metastases). Low-dose neuroleptics can also be used when benzodiazepines are not helpful or when there is the possibility of delirium, dementia, or other complications. Low-dose anticonvulsants (e.g., pregabalin, 200 mg per day) are sometimes used to treat severe treatment-resistant anxiety when other medications are ineffective or contraindicated because of certain associated risks.[26] Generally, the use of neuroleptics or anticonvulsants is considered after adequate trials with several first-line agents (e.g., SSRIs, SNRIs, and benzodiazepines) because of the significant side effect burden and potential for drug-drug interactions with these agents. Consultation with a psychiatric clinician is strongly recommended before these medications are used. Direct involvement of a psychiatric clinician is imperative for the management of patients receiving these medications.

The presence or absence of specific psychiatric or medical comorbidities is frequently a critical factor in the selection of pharmacological treatments. Pharmacokinetic and pharmacodynamic interactions with other medications are also important factors to be considered in the selection of agents. Following are some examples of such factors and clinical situations driving the selection of pharmacological treatments:

• When depressive symptoms are comorbid with anxiety, treatment with SSRIs, SNRIs, or other antidepressants is strongly considered.
• When neuropathic pain is comorbid with anxiety symptoms, specific antidepressants with known efficacy in treating neuropathic pain (e.g., duloxetine and venlafaxine) are considered.
• When hot flashes are comorbid with anxiety symptoms, specific agents with known efficacy in treating hot flashes (e.g., venlafaxine) are considered.
• Specific medications with known side effects (e.g., nausea with duloxetine or risk of sedation with mirtazapine) are avoided when patients are already experiencing these side effects from their cancer treatments and because of the possible exacerbation of these side effects.
• Treatment with significant CYP2D6 inhibitors (e.g., paroxetine) is not recommended when patients are receiving tamoxifen because of the risk of significant drug-drug interactions. (Refer to the PDQ summary on Fever, Sweats, and Hot Flashes for more information.)