Current Psychopharmacology - Volume 6, Issue 2, 2017

Background: Tianeptine is an atypical antidepressant marketed as Stablon since the late 1980's. While chemically very similar to tricyclic antidepressants, tianeptine was thought to have the apparently paradoxical mechanism of action of enhancing serotonin reuptake. However, recent data highlight a multimodal pharmacology for tianeptine including actions at glutamatergic synapses (inhibiting NMDA receptors and an indirect effect on AMPA receptors) coupled with agonist effects at mu opioid receptors (μ-receptors). Objective: We have reviewed clinical and preclinical data for tianeptine to provide a comprehensive study of its pharmacology. Results: Clinical trials show that tianeptine is at least as efficacious as first-line antidepressant treatments, with improved tolerability as it is significantly less prone to disrupting the patient's normal functionality. Tianeptine appears more efficacious in males than females, although these gender-specific differences may be accounted for by pharmacokinetics. Preclinical data suggest that the ability to stabilise glutamatergic neurotransmission may underlie tianeptine's ability to improve cognitive function and anxiety-related symptoms. Alternatively, μ-receptor activation of the mTOR signalling pathway could lead tianeptine to be a fastacting antidepressant. Agonist actions at μ-receptors could also explain the potential abuse liability and dependence issues seen with high dose tianeptine. Conclusion: Tianeptine itself is off patent, but it still holds much promise as an experimental tool yielding valuable insights into the molecular mechanisms underlying depression.

Background: Opioid dependence and death in America have reached epidemic proportions. Since 2000, we have seen an increase of over 3,000 percent in patients seeking treatment for substance use disorders. The “gold standard” for medically –assisted treatment, that is, Buprenorphine (a partial opioid agonist), combined with Naloxone, an opioid antagonist. Unfortunately, the relapse rates for Buprenorphine programs are high, and withdrawal reactions are common when Buprenorphine is precipitously discontinued. We must find approaches to treating substance use disorders that are more effective. Objectives: This report reviews the neuropharmacology of neurotransmitters involved in brain reward circuitry to increase understanding of the effect of Buprenorphine/Naloxone treatment on patients with substance use disorders. Discussion: We provide evidence, from animal and human models, regarding the acute and chronic effects of Buprenorphine on Dopaminergic reward processing. Microdialysis in animal models reveals that acute Buprenorphine tends to increase mesolimbic dopamine release. However, longterm use tends to decrease dopamine release. Cessation of Buprenorphine combination treatment increases drug reinstatement and relapse. Conclusions: This review of both the acute and chronic effects of Buprenorphine naloxone combination therapy on neurotransmission and behavior suggests new treatment targets and clinical options. “Pro-Dopamine Regulation” to induce dopaminergic homeostasis, via new options, other than the current, underutilized FDA approved Medication Assisted Treatments, which favor dopamine antagonism is proposed. We hypothesize that dopamine homeostasis is a crucial process that suppresses withdrawal symptoms, drug seeking and relapse in abstinent individuals.

Bipolar disorder is characterized by a host of sleep-wake abnormalities that suggests that the reticular activating system (RAS) is involved in these symptoms. One of the signs of the disease is a decrease in high frequency gamma band activity, which accounts for a number of additional deficits. Bipolar disorder has also been found to overexpress neuronal calcium sensor protein 1 (NCS-1). Recent studies showed that elements in the RAS generate gamma band activity that is mediated by high threshold calcium (Ca2+) channels. This minireview provides a description of recent findings on the role of Ca2+ and Ca2+ channels in bipolar disorder, emphasizing the involvement of arousal-related systems in the manifestation of many of the disease symptoms. This will hopefully bring attention to a much-needed area of research and provide novel avenues for therapeutic development.

Background: Recently, it was demonstrated in a series of experiments that a specifically designed odor inhaler outperformed well-known and popular stress relieving techniques. In another study it was shown that odor inhalers increased attention and concentration in a demanding cognitive task. Objective: This paper follows up on these experiments and investigates whether such effects can also be found for an inhaler specially designed to reduce pain. Method: Two prospective randomized, controlled cross-over documentary studies were conducted comparing participants' individual pain management (menstrual pain and chronic lower back pain) with an odor inhaler used as an adjuvant. Results: The odor inhaler improved pain dynamics like onset of pain and pain duration for both menstrual pain and lower back pain in a natural setting. In individuals suffering from chronic lower back pain, the inhaler also increased the pain alleviating effect of the individual pain management method. In both studies mood and well-being were considerably increased when the inhaler was applied. No side effects were reported. Conclusions: Even highly effective individual pain-relieving methods benefit from the use of this odor inhaler by changing pain dynamics and improving pain relief. Therefore, it helps to facilitate and amplify pain management.

Background: While negative symptoms are a significant barrier to successful recovery in patients with schizophrenia, their pharmacotherapy by adjunctive antidepressants has produced unpredictable results. Objective: In the present study, some of the native methodical published studies have been the subject of a new meta-analysis to evaluate the usefulness of add-on antidepressants on negative symptoms of schizophrenia. Method: Following searching in known databases, eight homemade relevant randomized clinical trials, including 277 male participants, had been selected. All the samples had been chosen among the chronic male inpatients, meeting the diagnosis of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision, who had been entered into parallel group, double-blind studies for random assignment to an antidepressant or placebo plus their current antipsychotic. Scale for Assessment of Negative Symptoms was used as the primary outcome measure in these experiments for assessment of negative symptoms. Response, too, was defined as a reduction of ≥20% in the score of the aforesaid scale (total and/or subscales). Results: Combined Effect Size of the aforesaid studies has revealed a significant influence with regard to the effectiveness of antidepressants on negative symptoms of schizophrenia (OR = 7.00, CI= 3.79 - 12.93, z= 7.49, p<0.000). Comparable consequences too could be found with regard to different symptoms of deficit syndrome. Anhedonia -Asociality displayed the best Combined Effect Size, followed by Affective Blunting, Avolition -Apathy, Attention Deficit, and lastly Alogia. Heterogeneity of all the abovementioned analysis was negligible and thus suitable. Conclusion: Antidepressants have favorable effects with respect to the improvement of deficit syndrome and its different symptomatic dimensions.

Background: Elevated levels of testosterone have been mentioned to affect sleep quality and increase the risk on developing insomnia. The second (index finger, 2D) to fourth (ring finger, 4D) digit ratio (2D:4D) is a biological correlate for prenatal testosterone and estrogen exposure. Objective: The objective of this study was to investigate the possible relationship between the 2D:4D digit ratio and insomnia, sleep quality, and total sleep time. Methods: A survey was held among N=557 Dutch students. In addition to demographic data, a subscale of the Dutch SLEEP-50 questionnaire was completed, assessing insomnia symptoms experienced over the past 4 weeks. For both hands, the 2D:4D ratio was assessed using digital Vernier calipers. Results: Data from N=143 men and N=366 women was analyzed. Their mean (SD) age was 20.8 (2.6). N=21 men and N=54 women scored above the cut-off point (≥ 19) for insomnia (average score 22.5 ± 3.4). Overall, no significant correlations were found between the digit ratio of either hand and insomnia, sleep quality, or total sleep time. In men, a significant correlation was found between the right 2D:4D ratio and total sleep time (r=0.173, p=0.039). No significant effects were found in women. Conclusion: No significant associations were found between the 2D:4D digit ratio and insomnia.

Objective: The present study provides the first published data documenting associations between self-reported executive functioning competencies and retrospective accounts of psychiatric medication usage. Background: Executive functioning competencies in planning, organizational skills, inhibitory control, selective attention, and optimal cognitive-set maintenance are essential to attain and sustain optimal problem-solving and goal pursuit. Executive functioning deficits have been observed with some regularity in the aftermath of major neurological or developmental traumas through the use of performance-based tests. However, executive functioning assessment research is being extended to self-report indices that measure perceived skill competencies associated with psychiatric conditions such as depression and attention disorders. Methods: A sample of national respondents (N = 595) was gathered through the use of Amazon's Mechanical Turk. Participants responded to the Executive Functioning Index (EFI) and a survey of psychiatric interventions. Results: Researchers found around a quarter of this national sample have relied on more than two of nine different psychiatric medications at some point during their lifetimes. Motivational drive seemed to have the greatest relative risk estimates (RR = 3.58) for all of the criterion variables. While gender differences in medication use were common, interactions with high risk executive functioning groups were rarely found. Conclusion: A longitudinal study examining the Executive Functioning-Symptom- Medication nexuses would be the next step in the understanding of how executive functioning deficits relates to psychiatric treatment including directionality and mediating factors. This area of executive functioning assessment has the potential to aid in prevention and earlier treatment to alleviate the intensity of symptoms that produce distress and impairment.

Background: Methamphetamine (MA) is an anxiogenic drug that is abused by adolescents for whom there is a risk of later developing high anxiety. This risk may be reduced by concomitant environmental enrichment which can reduce anxiety in laboratory rodents. Objective: As enrichment can attenuate anxiogenic effects of other drugs such as amphetamine sulfate and scopolamine, the present study aimed to determine if MA treatment of adolescent rats would affect their later level of anxiety, and if the outcome could be modified by exposure to enrichment. Methods: Male and female PVG/c hooded rats received 2 mg/kg/day of MA for 10 consecutive days during late adolescence (41-50 days after birth) while housed in standard or enriched cages (containing objects) before and during drug treatment and before and during testing in young adulthood, when anxiety-related behavior was recorded in a light-dark box and an elevated plus maze, as well as the rats' responsiveness to a novel Y-maze arm. Results: MA-treated rats from standard cages showed increased anxiety suggested by their longer emergence latencies into the light side of the light-dark box and no significant preference for entering a novel Y-maze arm. The lack of a similar drug effect for males from enriched cages suggested that enrichment attenuated their subsequent MA-related anxiety. Conclusion: Late adolescent treatment with MA increased later anxiety which, for males only, can be attenuated by exposure to enrichment during and following late adolescence. Consequently, deleterious effects of MA abuse on adolescent emotional development might be reduced by appropriate enrichment.