The use of alternative therapies has increased substantially over the last decade, particularly for more chronic conditions such as anxiety. Among the most widely used treatments are medicinal herbs, or phytomedicines, such as kava (Piper methysticum), which has demonstrated anxiolytic activity in both animal models and clinical samples. Kava has several advantages over conventional pharmacologic treatments for anxiety—in clinical settings it has been associated with better tolerability and lack of physiologic dependence and withdrawal. However, phytomedicines are not rigorously regulated in the United States and systematically collected safety data are very limited. These issues are a leading concern regarding the safety of medicinal herbs such as kava. In this report, the safety profile for kava is provided, including findings from a study of its use in generalized anxiety disorder. Safety parameters assessed include occurrence of adverse events, withdrawal symptoms, effect on heart rate, blood pressure, laboratory assessments, and sexual function. No differences were found between kava and placebo on any of the parameters evaluated. The data support the safety of kava in treating anxiety at 280 mg kava lactones/day for 4 weeks.

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.

Subjective cognitive complaints of women exposed to intimate partner violence (IPV) and nonabused women were examined using the Cognitive Difficulties Scale (CDS). Cognitive complaints were compared among victims of IPV with a lifetime diagnosis of posttraumatic stress disorder (PTSD) (PTSD+; n=20), victims of IPV without lifetime PTSD (PTSD-; n=21), and a nonabused comparison group (n=22). The results indicated that both the PTSD+ and PTSD- groups had significantly higher levels of self-perceived cognitive difficulties than nonabused women. Furthermore, PTSD symptom severity was found to be positively correlated with self-perceived cognitive difficulties (r=.47). Further research is needed to determine whether cognitive complaints are associated with exposure to IPV, with the subsequent development of PTSD, or with other not yet understood factors. Furthermore, additional work is needed to resolve whether cognitive complaints are accompanied by objective evidence of cognitive dysfunction in victims of IPV.

The search for novel anxiolytics and antidepressants has focused on compounds with the potential to reduce excessive hypothalamic-pituitary-adrenal (HPA) axis activity. L-glutamate, an excitatory neurotransmitter ubiquitously present within the central nervous system, conceivably plays an important role in activating the neural sites involved in stress modulation. Deactivation of the HPA axis by glutamatergic neurotransmission modulation may represent a novel therapeutic approach. Accordingly, the acute intravenous effects of the novel metabotropic (mGlu2/3) agonist LY354740 were tested on bonnet macaques (Macaca radiata) undergoing acute infusions of yohimbine, a noradrenergic stimulant. Dependent measures were the magnitude of the increase of plasma cortisol and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) customarily elicited by yohimbine. Next, the effects of 6 weeks of chronic oral administration of LY354740 on baseline (postcapture) plasma cortisol and MHPG levels in comparison to the identical measure in untreated controls were assessed. Subjects chronically treated with LY354740 received yohimbine infusions which were compared to yohimbine infusions and saline infusions in non-LY354740-treated subjects. Preliminary evidence supports the view that acute LY354740 infusion resulted in a marked diminution of yohimbine-induced stress response, as manifest by a substantial attenuation of cortisol and MHPG response observed in comparison to the saline-treated yohimbine condition. Chronic oral administration of LY354740 led to postcapture baseline cortisol levels which were markedly reduced (∼50%) in comparison to untreated control subjects; however, there were no significant parallel differences in MHPG levels. Yohimbine infusions elicited an increase in cortisol and MHPG levels in both LY354740-treated and non-LY354740-treated subjects, in comparison to declines in cortisol values observed following vehicle infusions (group X time interaction; P<.0001). Chronic LY354740-treated subjects failed to achieve cortisol levels comparable in range to those of untreated subjects primarily because of their low baseline cortisol levels. In contrast, despite equivalent baselines, yohimbine-induced MHPG values were increased overall in the chronically treated group compared to the saline and yohimbine-alone groups. Thus, LY354740 markedly reduced the acute corticoid and noradrenergic response elicited by yohimbine infusion. Chronic administration of LY354740 appears to present a safe and effective mechanism to markedly down-modulate the HPA axis while retaining noradrenergic responsivity.

In this paper, we review research utilizing postmortem brain tissue in order to investigate the potential neuropathology of the noradrenergic system in psychiatri disorders. The postmortem tissue approach to the study of the noradrenergic system has been used primarily in investigations of the biology of suicide and depression. Findings from postmortem studies provide data generally consisten with the hypothesis that a norepinephrine deficiency exist depression, and possibly in the victims of suicide. However postmortem studies do not presently provide irrefutable evidence of noradrenergic neuropathology. Technical shortcomings, issues of reproducibility, and the strengths postmortem research are reviewed. More rigorously performed postmortem research is needed to aid researchers in pinpointing specific neuropathologies associated with psychiatric disease.

Studying brainstem auditory evoked potentials (BAEPs) and comparing the specific waves in smokers vs nonsmokers in both positive- and negative-symptom schizophrenia may elucidate the role of smoking in information processing. BAEPs were recorded in 40 patients with schizophrenia; 20 had predominantly positive symptoms (10 smokers and 10 nonsmokers) and 20 had predominantly negative symptoms (10 smokers and 10 nonsmokers). The severity of positive and negative symptoms was assessed by scale of assessment of positive symptoms and scale of assessment of negative symptoms (SANS). The BAEP results were compared with 15 healthy control individuals matched with the patients by age, sex, and cultural background. The smokers with negative symptoms showed a significant increase in the alogia, summary, and composite scores of SANS as compared to the nonsmokers. Although, most of the BAEP abnormalities were among patients with positive symptoms. The effect of smoking on the BAEPs was only in patients with negative symptoms.

We also studied the interaction between smoking factor (smokers vs nonsmokers) and group type (group with mostly positive symptoms vs group with mostly negative symptoms) on the BAEPs and found a significant difference only for the first-wave latency mainly on the right side (P=0.012). The absence of a significant effect of smoking on most of the parameters of the BAEPs on interaction with the group factor suggests that the effect of smoking on the BAEPs is more apparent when negative symptoms prevail. However, studies are warranted to substantiate this finding.

This report describes the psychometric properties of the Self-Assessment of Resilience and Anxiety (SARA) scale within the context of a study of kava for generalized anxiety. This eight-item, patient-rated scale includes questions designed to measure calmness, mental clarity, confidence, physical well being, sociability, and resilience. The SARA scale was administered during a clinical trial of kava versus placebo in 38 subjects diagnosed with generalized anxiety disorder (GAD). Validation of the SARA scale was assessed against the Hamilton Rating Scale for Anxiety, Hospital Anxiety and Depression Scale, Penn State Worry Questionnaire, Sheehan Disability Scale, Arizona Sexual Experience scale, and Clinical Global Impression of Illness Improvement scale. Good test-retest reliability, internal consistency, convergent validity, and sensitivity to treatment were identified, and factor analyses revealed a three-factor internal structure. The SARA scale was responsive to symptom change over time and correlated with comparable GAD symptom measures. The SARA scale demonstrates solid psychometric properties and may serve as a reliable and valid measure in the use of kava or related medicinal herbs.

Treatment of acute mania has been greatly influenced by loading strategies. Loading has potential benefits, including rapid symptom reduction in mania and a shortened length of stay. Disadvantages include an increased likelihood of adverse effects of the medications. Loading strategies for lithium, valproic acid (divalproex sodium), carbamazepine, oxcarbazepine, olanzapine, and haloperidol decanoate in the treatment of acute mania are discussed. Recent studies high-light this treatment option for selected patients. It is the unique properties of the medications that influence their use in loading. Issues in patient selection for loading strategies with each medication are also considered.