Faculty Bibliography

Although numerous effective antidepressant medications are available, many patients suffer multiple episodes that are not adequately controlled with presently available therapies. Up to 1.5% of the general population is estimated to have chronic, severe depression. Approximately 30% of these patients are medically resistant to present treatments. As a result, combination treatments of antidepressants with other medications (ie, so-called augmentation strategies) are frequently employed for partial or nonresponders to various monotherapies, including serotonin selective reuptake inhibitors (SSRIs). Now comes a study of the high-affinity nicotinic acetylcholine receptor antagonist mecamylamine hydrochloride as an augmenting agent for treatment of major depressive disorder (MDD) in patients who are partial responders to SSRIs. While quite preliminary, this appears to be the first published report on the use of a central, high-affinity nicotinic antagonist for the augmentation of SSRIs in partial responders. Interestingly, it is well known that approximately 50% of patients with MDD are cigarette smokers, with smoking believed to exert antidepressant and anxiolytic effects. Clearly these results are early and require the completion of this and other studies for validation; however, the use of drugs targeting the nicotinic receptor for the treatment of depression is a novel approach worthy of further attention.

While the prevalence of bipolar disorder is roughly equal in women and men, the course of illness tends to be more severe in women. In 50% of women with bipolar disorder, illness onset occurs at or within 1 year of menarche. Despite this pattern, most women with bipolar disorder are not accurately diagnosed until they have had a child and developed an episode of PPD. The occurrence of PPD in a patient with recurrent depression but no history of mania or hypomania should raise the index of suspicion for the presence of an underlying bipolar disorder. Medications used in the treatment of bipolar disorder can result in side effects, such as sexual dysfunction or weight gain, and in drug-drug interactions. Carbamazepine, oxcarbazepine, and topiramate can reduce the effectiveness of oral contraceptive pills while sodium valproate may be associated with polycystic ovary syndrome, which is the most common cause of menstrual disturbance in women of reproductive age. Contrary to popular belief, pregnancy does not protect against bipolar disorder relapse. Thus, physicians must be proactive in protecting the mother from relapse. In general, physicians should use nonpharmacologic measures as much as possible, pharmacology when necessary, and consider electroconvulsive therapy when the risks of medications are too great. Psychotic, floridly manic, or profoundly depressed patients should be given medication, for which information concerning safety during pregnancy and breastfeeding exist. For less severe problems, nonpharmacologic strategies can be employed and include promoting the maintenance of healthy nutrition and activity, protecting social and activity/sleep rhythms, educating patients and their families on how to recognize a prodrome of illness, and the use of cognitive-behavioral therapy to address mild symptoms of anxiety, depression, or substance abuse.

Anxiety disorders are highly prevalent, are increasing in incidence, affect individuals early in life, and significantly impact health care and quality of life. As such, they are serious public health problems that deserve attention now and in the future. Over the last 10-20 years, there has been marked improvement in pharmacologic and psychosocial interventions for anxiety. Due to their broad spectrum of efficacy against common comorbidities and lack of association with abuse and dependence, serotonergic and mixed serotonergic noradrenergic antidepressants are first-line therapies for anxiety disorders. Benzodiazepines are still widely used in clinical practice because they are well tolerated and work quickly and effectively. Other medications that are emerging as potentially useful for selected populations with anxiety include atypical neuroleptics and anticonvulsants. Cognitive-behavioral therapy (CBT) is at least as effective as medication for many patients with anxiety disorders and facilitates maintenance of benefit over the long term. Resilience, the capacity to bounce back from adversity, can be reliably measured with a psychometrically valid scale, the Connor-Davidson Resilience Scale. Compared with the general population, individuals with anxiety disorders exhibit decreased resilience. Studies have shown that pharmacologic treatment combined with CBT may increase resilience within 2-3 months. Emerging neurobiologic research indicates that noradrenergic pathways and 5-HT2 transporter efficiency may mediate effects on resiliency.

Bipolar disorder is underdiagnosed and often mistaken for unipolar depression. Bipolar patients spend 33% of their time in a state of depression compared to 11% of time spent in a manic state. Duration of time depressed and severity of depression are associated with increased risk for suicide, which occurs in 10% to 20% of bipolar patients. Antidepressants are increasingly being used as adjuncts in the depressed phase of bipolar disorder, although they provide a moderate risk for switch into mania. Lithium and some antiepileptics and atypical antipsychotics have shown antidepressant effects in the treatment of bipolar disorder. Other adjuncts for treatment-refractory patients include monoamine oxidase inhibitors and electroconvulsive therapy

BACKGROUND: Evidence suggests that the newer antidepressant drugs may differ with respect to their effects on body weight, especially during long-term treatment. However, the published data about treatment-emergent weight change with the newer antidepressants are limited. Most reports of unexpected selective serotonin reuptake inhibitor (SSRI)-associated weight gain are anecdotal or from small controlled trials. To determine if differences exist among the newer antidepressants, the authors retrospectively analyzed data from clinical trials comparing nefazodone with SSRIs and with imipramine. METHOD: Weight change data supplied by Bristol-Myers Squibb from 6 completed clinical trials comparing the antidepressant nefazodone (N = 523) with 3 SSRIs, fluoxetine, sertraline, and paroxetine (N = 513), as well as 3 trials comparing nefazodone (N = 225) with the tricyclic antidepressant imipramine (N = 224) were analyzed. In all studies, nefazodone was found to be equal in efficacy to the comparator antidepressants. Studies that included both acute and long-term treatment phases were included in the analysis. Acute phases of the trials lasted either 6 or 8 weeks, and long-term phases varied in duration from 16 to 46 weeks. The analysis included summarizing the number and percentage of patients in each group with a > or = 7% change in body weight from baseline at any point in the long-term and acute phases, at endpoint, and at week 16 of the long-term phases. RESULTS: Using 7% or greater weight change as the measure of clinical significance, 4.3% of SSRI-treated patients had lost weight at any point in the acute phase versus 1.7% of those treated with nefazodone (p = .017). However, at any point during the long-term phase, significantly more SSRI-treated patients than nefazodone-treated patients showed a significant increase in body weight (17.9% vs. 8.3%; p = .003). At any point in the acute phase, significantly more imipramine-treated patients than nefazodone-treated patients had a 7% or greater increase in body weight (4.9% vs. 0.9%; p = .027), and for the long-term phase the comparison yielded 24.5% versus 9.5%. The difference during the long-term phase was statistically significant in women (p = .017), but not in men (p = .078) due to the small numbers of men in each group. CONCLUSION: SSRIs caused more weight loss during short-term treatment but more weight gain during long-term treatment. These results lend support to the observation that some antidepressants have a greater expected risk of weight gain than others during long-term therapy

Antiepileptic drugs (AEDs) have a broad range of activity in the central nervous system and can thus be expected to have multiple clinical effects. Older AEDs have been used in psychiatry for some time. Introduction of the new AEDs within the last decade has been followed by reports of their efficacy in patients who had failed the more established treatment regimens. It has become evident that drugs such as gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, zonisamide, and tiagabine have beneficial safety and cognitive profiles and appear to be well tolerated by patients. While there are an increasing amount of data available indicating that these drugs may be effective in treating certain aspects of anxiety disorders, depression, and bipolar disorder, still not enough is known about all of their potential uses. It is difficult for clinicians to evaluate and use these drugs in the absence of clinical trials. Until more studies are done to increase the evidence base for the effectiveness of these agents, we have to rely on observations from community practice and personal experiences in making treatment choices

Reviewed the literature discussing weight gain and loss as side effects of psychotropic drugs. Such psychotropic drugs include antidepressants (selective serotonin reuptake inhibitors [SSRIs], nefazodone hydrochloride, venlafaxine hydrochloride, mirtazapine, and bupropion hydrochloride), antipsychotics, and mood stabilizers (lithium, valproate sodium, carbamazepine, gabapentin, lamotrigine, and topiramate). Causes of weight gain include decreased metabolic rate, increased food intake, and reduced physical activity. Few studies address the prevalence and extent of weight changes associated with treatment of psychiatric disorders. Clinical trials do not always comprehensively examine weight changes, especially delayed weight gain. Studies showed that SSRIs can induce short-term weight loss, which can be therapeutic, but that the drug is associated with long-term weight gain.

Discusses selective serotonin reuptake inhibitors (SSRIs) and their side effects. Side effects are typically categorized by organ system involvement (e.g., hematologic, nervous, renal) and frequency of occurrence (e.g., frequent, infrequent and rare). There could be 1 of 4 side effects: early onset-time limited, early onset-persistent, later onset, and withdrawal-emergent. Sexual dysfunction and weight gain can also be associated with SSRI use. The exact incidence, cause or causes, and optimal management of each of these side effects need to be determined. One potential outcome from studies of these side effects is that this research may reveal the underlying physiological mechanisms that mediate drug effects on appetite and sexual functions.