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1.
Curr Drug Targets ; 20(2): 182-191, 2019.
Article in English | MEDLINE | ID: mdl-28302034

ABSTRACT

Throughout the world, antidepressants (AD) and phosphodiesterase-5 inhibitors (PDE-5i) are the commonly prescribed psychopharmacological agents for treating patients with co-morbid mental health problem and sexual dysfunction (SD). The serotonergic and noradrenergic ADs, although effective, are not without any SD adverse-effects, especially erectile dysfunction (ED). ED is a failure to obtain a satisfactory erection for rewarding sexual coitus during the phases of male's sexual arousal. It is recognized as an important reason why non-adherence to treatment was observed in patients who were on AD. AD intervention caused remission to some of the pre- treatment psychopathology of ED. However, in many patients, AD potentially magnified the unwanted sexual sideeffects. This made the situation challenging for the mental health professional. These challenges are based on the complexity of ED, its etiology and the associated risk factors, which further add to its AD side-effect. The neuro-psychopharmacological basis for AD treatment selection was deliberated. Bio-psycho-social interventions are recommended at two pivotal stages. Firstly, a step should be taken for proper assessment (e.g. detailed history, psychosocial and laboratory investigations); and identify few modifiable risk factors for ED and associated mental health issues. Secondly, with guidance of an algorithm pathway, a practical intervention should include strategies such as dose reduction, augmentation or changing to an AD with lesser or no sexual adverse-effects. It is recommended that bupropion and mirtazepine to be prescribed when patients develop adverse sexual effects with serotonin selective reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI) and tricyclic antidepressant (TCA). Few suggestions which may be borne in mind are revising sexual scripts and improving sexual techniques, life-style modifications, psychotherapy and other nonpharmacological approaches which may be beneficial to both patients and their partners.


Subject(s)
Antidepressive Agents/therapeutic use , Erectile Dysfunction/drug therapy , Mental Disorders/drug therapy , Phosphodiesterase 5 Inhibitors/therapeutic use , Comorbidity , Drug Substitution , Erectile Dysfunction/psychology , Humans , Male , Medication Adherence , Mental Healing
2.
Curr Drug Targets ; 19(8): 907-915, 2018.
Article in English | MEDLINE | ID: mdl-28494749

ABSTRACT

In the past decade, many studies have highlighted the role of metabotropic glutamate receptor subtype 5 (mGlu5) modulators in attenuating alcohol-related biological effects such as alcohol consumption, alcohol-seeking and relapse-like behaviors. Taken together, these findings suggest that pharmacological agents acting at mGlu5 could be promising tools in curbing inebriation. mGlu5s are present abundantly in brain regions known to be involved in emotion regulation, motivation and drug administration. On a cellular level, they are primarily located at the postsynaptic part of the neuron where the receptor is functionally linked to various downstream proteins that are involved in cell signaling and gene transcription that mediate the alcohol-induced neuroplasticity. As well, the discovery of a functional link between mGlu5 and a specific isozyme, Protein Kinase C epsilon (PKCε) in mediating the attenuating effects of selective negative allosteric modulators of mGlu5 such as methyl- 6(phenylethynyl)pyridine (MPEP) and 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP) has sparked interesting speculations. In this article, we shall review the following: the effects of acute and chronic alcohol intake on mGlu5 signaling; the effects of mGlu5 ligands on alcohol-related neurobehavioral changes that are currently being studied both at pre-clinical and clinical stages; and the mechanisms underlying the pharmacological effects of these drugs.


Subject(s)
Alcohol Drinking/prevention & control , Alcoholism/drug therapy , Receptor, Metabotropic Glutamate 5/drug effects , Alcohol Deterrents/pharmacology , Alcohol Drinking/epidemiology , Alcoholism/physiopathology , Animals , Brain/drug effects , Brain/metabolism , Drug-Seeking Behavior , Humans , Ligands , Neurons/drug effects , Receptor, Metabotropic Glutamate 5/metabolism , Signal Transduction/drug effects
3.
Curr Drug Targets ; 19(12): 1352-1358, 2018.
Article in English | MEDLINE | ID: mdl-28025939

ABSTRACT

Sexual dysfunctions are commonly seen in women on selective serotonin reuptake inhibitors (SSRIs). The complexities of female sexual functioning are reflected through modulation of inter- playing factors like the neuropsychophysiological factors, inter-personal and relationship issue, psychiatric co-morbidities and physical disorder. The incidence of SSRIs-induced FSD is difficult to estimate because of the potential confounding effects of SSRIs, presence of polypharmacy, marital effect, socio-cultural factors and due to the design and assessment problems in majority of the studies. The exact mechanism of FSD-induced SSRIs is unknown. It has been postulated that although SSRIs may modulate other neurotransmitter system such as nitric oxide (NO), noradrenergic and dopamine in inducing FSD. In the present review, we highlight current evidence regarding potential mechanism of SSRIs in causing FSD, which include low sexual desire (low libido), arousal difficulties (lack of lubrication), and anorgasmia. The specific association of FSD to SSRI use, has not been ellucidated. The relationship is dose-dependent, and may vary among the groups with respect to mechanism of serotonin and dopamine reuptake, induction of release of prolactin from the pituitary gland, anticholinergic side-effects, inhibition of NO synthesis and emotional-memory circuit encryption for sexual experiences. Various interventional strategies exist regarding the treatment of SSRI-induced FSD and this includes tolerance, titration dosage, substitution to another antidepressant drug and psychotherapy. There is a need of better understanding of SSRIs-induced FSD for better treatment outcome.


Subject(s)
Selective Serotonin Reuptake Inhibitors/adverse effects , Sexual Dysfunction, Physiological/chemically induced , Sexual Dysfunction, Physiological/drug therapy , Dopamine/metabolism , Female , Humans , Norepinephrine/metabolism , Serotonin/metabolism , Serotonin Antagonists/pharmacology , Serotonin Antagonists/therapeutic use
4.
Curr Drug Targets ; 19(8): 916-926, 2018.
Article in English | MEDLINE | ID: mdl-28228081

ABSTRACT

Vaginismus is an involuntary muscle contraction of the outer third of vaginal barrel causing sexual penetration almost impossible. It is generally classified under sexual pain disorder (SPD). In Diagnostic and Statistical Manual, 5th edition (DSM-5), it is classified under the new rubric of Genito-Pelvic Pain/Sexual Penetration Disorder. This fear-avoidance condition poses an ongoing significant challenge to the medical and health professionals due to the very demanding needs in health care despite its unpredictable prognosis. The etiology of vaginismus is complex: through multiple biopsycho- social processes, involving bidirectional connections between pelvic-genital (local) and higher mental function (central regulation). It has robust neural and psychological-cognitive loop feedback involvement. The internal neural circuit involves an inter-play of at least two-pathway systems, i.e. both "quick threat assessment" of occipital-limbic-occipital-prefrontal-pelvic-genital; and the chronic pain pathways through the genito-spinothalamic-parietal-pre-frontal system, respectively. In this review, a neurobiology root of vaginismus is deliberated with the central role of an emotional-regulating amygdala, and other neural loop, i.e. hippocampus and neo-cortex in the core psychopathology of fear, disgust, and sexual avoidance. Many therapists view vaginismus as a neglected art-and-science which demands a better and deeper understanding on the clinico-pathological correlation to enhance an effective model for the bio-psycho-social treatment. As vaginismus has a strong presentation in psychopathology, i.e. fear of penetration, phobic avoidance, disgust, and anticipatory anxiety, we highlighted a practical psychiatric approach to the clinical management of vaginismus, based on the current core knowledge in the perspective of neuroscience.


Subject(s)
Dyspareunia/physiopathology , Sexual Dysfunction, Physiological/physiopathology , Vaginismus/physiopathology , Animals , Chronic Pain/physiopathology , Dyspareunia/psychology , Female , Humans , Sexual Dysfunction, Physiological/psychology , Sexual Dysfunctions, Psychological/physiopathology , Sexual Dysfunctions, Psychological/psychology , Vaginismus/psychology
5.
Compr Psychiatry ; 75: 94-102, 2017 05.
Article in English | MEDLINE | ID: mdl-28342379

ABSTRACT

OBJECTIVE: To understand the needs of patients with schizophrenia for recovery, this study examined the type and level of social support and its association with quality of life (QOL) among this group of patients in the city of Kuala Lumpur. METHOD: A cross-sectional study was conducted on 160 individuals with schizophrenia receiving community psychiatric services in Hospital Kuala Lumpur (HKL). The WHOQOL-BREF, Brief Psychiatric Rating Scale (BPRS) and Multidimensional Scale of Perceived Social Support (MSPSS) were used to assess QOL, severity of symptoms and social support, respectively. The study respondents were predominantly Malay, aged less than 40, males, single, unmarried, had lower education levels and unemployed. RESULTS: About 72% of the respondents had poor perceived social support, with support from significant others being the lowest, followed by friends and family. From multiple regression analysis, social support (total, friend and family) significantly predicted better QOL in all domains; [B=0.315 (p<0.001), B=0.670 (p<0.001), B=0.257 (p<0.031)] respectively in Physical Domain; [B=0.491 (p<0.001), B=0.735 (p<0.001), B=0.631 (p<0.001)] in Psychological Domain; [B=1.065 (p<0.001), B=0.670 (p<0.017), B=2.076 (p<0.001)] in Social Domain and; [B=0.652 (p<0.001), B=1.199 (p<0.001), B=0.678 (p<0.001)] in Environmental Domain. Being married and having shorter duration of illness, lower BPRS (total) scores, female gender and smoking, were also found to significantly predict higher QOL. CONCLUSION: Social support is an important missing component among people with schizophrenia who are already receiving formal psychiatric services in Malaysia.


Subject(s)
Community Mental Health Services/statistics & numerical data , Quality of Life/psychology , Schizophrenia/therapy , Schizophrenic Psychology , Social Support , Adult , Brief Psychiatric Rating Scale , Cross-Sectional Studies , Female , Humans , Malaysia , Male , Middle Aged , Surveys and Questionnaires
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