The increased suicide risk in the first year of treatment mandates that follow-up psychiatric treatment should be well-designed and reliable. The ongoing suicide risk assessment of patients with depression should give special valence to accompanying anxiety, and its presence may call for increased monitoring or hospitalization.
Pharmacological management of patients with mixed anxiety-depression might include benzodiazepines, but their risks of sedation and dependence must be considered. Although many of the SNRIs and SSRIs have received separate indications for various anxiety disorders, there may be differential responses to these medications. For instance, one study reported better outcomes with the SNRI venlafaxine than with the SSRI fluoxetine(Drug information on fluoxetine) for patients with MDD and GAD.11 There may also be a role for other medications in patients with depression accompanied by anxiety, including low-dose atypical antipsychotics, anticonvulsants (divalproex, carbamazepine(Drug information on carbamazepine), gabepentin, lamotrigine(Drug information on lamotrigine), and topiramate(Drug information on topiramate) have shown effects in smaller studies), and buspirone(Drug information on buspirone).6 β-Blockers are useful in blocking peripheral manifestations of anxiety, but caution is advised when treating depressed patients because of the possible depressogenic effect.
Dissociative phenomena and their relationship to TRD
In the evaluation and treatment of patients with depression, dissociation in one of its many forms is easily overlooked as a contributing factor for treatment resistance. In DSM-IV-TR, dissociative disorders are Axis I disorders in which there are significant disruptions in memory, consciousness, identity, or the perception of the environment. There are currently 5 dissociative diagnoses in DSM-IV-TR: dissociative identity disorder (formerly known as multiple personality), dissociative amnesia, dissociative fugue, depersonalization disorder, and dissociative disorder not otherwise specified (NOS).
A thorough psychiatric evaluation includes screening questions for dissociative phenomena, especially when a patient presents with a known history of trauma or abuse. However, patients may not be open about abuse histories and may also fail to spontaneously disclose dissociative experiences, especially if the focus of the evaluation is on mood symptoms. Psychiatrists who treat large numbers of patients with dissociative disorders find that in many, the condition has been undiagnosed for a number of years.
Depression and dissociative disorders both represent final common pathways for patients who have suffered abuse in childhood or have undergone traumatic incidents as adults. For this reason, when a patient has such a history, it may be important to consider using a structured interview for dissociative disorders, such as the Structured Clinical Interview for DSM-IV (SCID-D), or a screening tool, such as the Dissociative Experiences Scale.12
Using these instruments, one inpatient study of 171 consecutively admitted patients to a state hospital in Massachusetts found that 15% of these patients met criteria for a dissociative disorder. In this study, the most common dissociative diagnoses were dissociative identity disorder, dissociative amnesia, and dissociative disorder NOS. Furthermore, and relevant for considerations of TRD, there was a high rate of comorbid depressive illness among the patients with the various dissociative disorders.13
Dissociative phenomena can be mistaken for psychosis. Marcum and colleagues14 reported the case of a 29-year-old man who had failed to respond to a high-dose antidepressant and antipsychotic regimen for what was presumed to be a major depression with psychotic features. This patient had experienced childhood sexual abuse at the hands of an older brother. A sodium amytal interview gave strong evidence for dissociative identity disorder, and the patient subsequently responded to hypnotherapeutic sessions, with a marked decrease in depressive symptoms and normalization of biological markers for depression.
The role of sleep disorders in TRD
Disturbance of sleep is a common complaint among patients with MDD and other Axis I disorders. In the initial treatment approach for a patient who presents with insomnia and depressed mood, a sedative/hypnotic or low-dose trazodone at bedtime is often used to supplement the main full-dose antidepressant. Usually, sleep quality and quantity improve with depression. However, when mood symptoms fail to respond to adequate psychotropic management or psychotherapy, TRD should be suspected. Further workup for comorbid medical issues or review of the differential diagnoses is necessary.
Multiple factors related to sleep may contribute to poor response in depression treatment. Lack of exercise, insufficient time for sleep, shift work, and disruptive drugs and substances (eg, excessive or ill-timed use of alcohol(Drug information on alcohol) and caffeine(Drug information on caffeine)) can lead to poor sleep quality, daytime sleepiness, or fatigue.
Perhaps less identified in psychiatry offices are sleep-related breathing problems—most commonly obstructive sleep apnea (OSA). OSA is a sleep disorder characterized by repeated obstruction of the upper airways resulting in apnea (complete) or hypopnea (partial), with corresponding oxygen desaturations and arousals from sleep.15