MOOD DISORDERS:
SOME THERAPEUTIC OPTIONS

     Avoiding the more complicated issues innate to accurate differential psychological diagnosis of anxiety disorders, the focus of this section is the pharmacology of medications used for anxiety and other mood disorders. Anxiety may also arise from a number of physical disorders like hyperthyroidism that must be excluded by physical and laboratory evaluation. Various members of the extended TCA and SSRI families discussed in the section on depression have been FDA-approved for post-traumatic stress disorder (PTSD), social phobias, panic disorder, and even more recently for premenstrual dysphoric mood disorder (PMDD) in the case of sertraline (May, 2002).  Other strategies are employed for bipolar disorder, which include not only lithium, but various combination regimens that may even include some anticonvulsants like carbamazepine, phenytoin, and more recently valproate.
     The fact remains that most of these agents are approved and used for other applications as well; so while the pharmacological science is the same, this section will discuss these agents as they may be used for problems other than mood disorders.  In addition to generalized anxiety disorder (GAD) and other psychological diagnoses complicated by anxiety, the benzodiazepines are used as anti-seizure agents, especially in the case of status epilepticus.  The ensuing section discusses other anti-seizure agents that might be used in mood disorders and even management of chronic neuropathic pain, but which are approved and primarily used in control of various seizure disorders.  Bear in mind that their use in treatment of mood disorders remains experimental in spite of significant success, especially in some cases of bipolar disorder.
     Benzodiazepines are widely prescribed, as extensive literature supports their use in patients with anxiety disorder; but whether they are the treatment of choice for patients with generalized anxiety disorder, a mild disturbance seen almost exclusively by family practitioners, is another issue. Study design to produce meaningful results is difficult, including recruitment of subjects from psychiatric populations, and severity of anxiety is clearly a significant factor influencing treatment response. The benzodiazepines may provide more benefit in moderate to high levels of anxiety or dysphoria; and while benzodiazepines may be effective in the short-term, TCAs could eventually prove superior GAD.
     The decision to medicate, especially with a benzodiazepine, must be carefully weighed, the severity and duration of symptoms and degree of psychosocial impairment against the individual addiction potential of the patient. Alcoholism has been proposed in some patients as developed as a form of self-medication of GAD, so while anxiolytic pharmacotherapy would be logical for such patients, the addiction potential of benzodiazepines might indicate that buspirone might be a better choice with its virtual lack of addiction potential.
     Clinical efficacy of the various benzodiazepines is virtually equal, but pharmacokinetics vary considerably. Onset of action is determined by rate of absorption and distribution, which is rapid and complete after oral administration of most benzodiazepines; but duration of action depends on half-life and the presence or absence of active metabolites. Those with long half-lives like diazepam can be administered once daily, while those with shorter half-lives like alprazolam may require multiple daily doses.  Agents with longer half-lives usually also show longer duration of action and are generally considered more appropriate for long-term therapy.  This TABLE provides some insight into the various benzodiazepines, their pharmacokinetic properties, and their common uses.
     Primary side effects include sedation, fatigue, poor concentration, ataxia, dysarthria and confusion; and administration to elderly patients can lead to falls. Of course they may impair the ability to drive or operate heavy machinery, an effect that is generally exacerbated by concurrent alcohol ingestion.  Disinhibition is not uncommon, while rage is observed on occasion.  These agents decrease rapid eye movement (REM) sleep, with significant rebound upon discontinuation.  All of the benzodiazepines are in Preganancy Category D. (For a thorough discussion of psychoactive agents and pregnancy, see this TABLE and this DISCUSSION.)  Buspirone, doxepin, hydroxyzine, and even propranolol have all been used successfully to control anxiety in situation when the benzodiazepines are deemed inappropriate.