Efficacy and Safety of Asenapine Versus Olanzapine in Combination With Divalproex for Acute Mania: A Randomized Controlled Trial.

BACKGROUND: Atypical antipsychotics are used for the treatment of acute mania, either as monotherapy or in combination with lithium or divalproex, which have a better tolerability profile as compared with typical antipsychotics. Asenapine, a newer atypical antipsychotic, has been found to be effective for the treatment of mania, with efficacy similar to olanzapine. The objective of the study was to compare the efficacy and safety of asenapine and olanzapine when used in combination with divalproex in patients with acute mania. METHODS: One hundred twenty patients aged 18 to 55 years, diagnosed with manic episode, were randomized to receive either flexible dose of sublingual asenapine (10-20 mg/d) or tablet olanzapine (10-20 mg/d), in combination with valproate 20 mg/kg per day for a period of 6 weeks. Efficacy was measured as change in Young Mania Rating Scale and Clinical Global Impression-Bipolar using intention-to-treat analysis with last observation carried forward, and safety was measured using Udvalg for Kliniske Undersøgelser scale and Modified Simpson-Angus Extrapyramidal Side Effects Scale. RESULTS: There was a significant reduction in Young Mania Rating Scale and Clinical Global Impression-Bipolar scores over time in both groups, with a significantly higher reduction in the olanzapine group as shown by the group × time interaction effect. Higher weight gain, increased sleep and appetite, and tremors were seen in the olanzapine-treated patients as compared with asenapine-treated patients; however, tongue hypesthesia was seen in the asenapine group only. CONCLUSIONS: This study found that asenapine was an effective and well-tolerated atypical antipsychotic alternative to olanzapine in combination with divalproex for the short-term management of acute mania.

Drug-induced diseases (DIDs): An experience of a tertiary care teaching hospital from India.

BACKGROUND & OBJECTIVES: Drug-induced diseases (DIDs) are well known but least studied. Data on DIDs from India are not available. Hence, this retrospective cross-sectional study was undertaken using suspected adverse drug reaction (ADR) data collected form Pharmacovigilance Programme of India (PvPI) to evaluate profile of DIDs over two years, in a tertiary care teaching hospital from north India. METHODS: The suspected ADRs in the form of DID were evaluated for drug and disease related variables and were classified in terms of causality. RESULTS: DID rate was 38.80 per cent. Mean duration of developing DIDs was 26.05 ± 9.6 days; 25.16 per cent had more than one co-morbid condition. Geriatric population (53.99%) accounted for maximum DIDs followed by adult (37.79%) and paediatric (8.21%). Maximum events were probable (93.98%) followed by possible (6.04%). All DIDs required intervention. Gastritis (7.43%), diarrhoea (5.92%), anaemia (4.79%), hypotension (2.77%), hepatic dysfunction (2.69%), hypertension (1.51%), myalgia (1.05%), and renal dysfunction (1.01%) were some of the DIDs. Anti tubercular treatment (ATT), anti retroviral treatment (ART), ceftriaxone injection, steroids, non-steroidal anti-inflammatory drugs, antimicrobials and anticancer drugs were found as commonly offending drugs. INTERPRETATION & CONCLUSIONS: Our findings show that DIDs are a significant health problem in our country, which need more attention.

Fatal adverse drug reactions: Experience of adverse drug reactions in a tertiary care teaching hospital of North India - A case series.

Medical burden of fatal adverse drug reactions (FADRs) is significant. The epidemiological data on FADR do exist from the western world, but there is scanty from India. We hereby report a case series of FADRs recorded in a 2 years period. Point prevalence of FADRs was 0.223%. Point prevalence of all cause death in the hospital was 1.20%. The drugs causing FADRs were injection bupivacaine, amphotericin B, directly observed treatment short-course Category-1, injection streptokinase, and tablet ferrous sulfate. All these FADR were labeled as possible expect one case as probable. All FADR were labeled as type A. In three out of five the central nervous system was involved, while the hepatic system and multiorgan failure accounted for one case each. Two cases each were acute and subacute, while one was latent in nature. Reporting of FADRs shall go a long way in patient safety.

Fixed drug combination (levosulpiride and rabeprazole)-induced atypical Parkinsonian's disorders with associated anxiety and low-lying depression.

We hereby describe a rare case of levosulpiride-induced atypical parkinsonism presenting with sluggish movements, atypical kinetic tremors (tremors with voluntary movement), periorbital tremors, dystonia, difficulty in speech and coordination, postural imbalance, with additional features of difficulty in swallowing and drooling with associated recent onset psychiatric disturbances such as anxiety and low-lying depression. The dechallenge of levosulpiride and medications for associated anxiety and low-lying depression caused a complete remission of the disease within 2 ½ months.

Does Coronavirus Disease 2019 Kill More Elderly Men than Women Due to Different Hormonal Milieu.

Preliminary data depicts a much greater prevalence and high case-fatality rate in advanced age males as compared to age-matched women with severe acute respiratory syndrome-coronavirus-2 infections with high morbidity, mortality, high referral, and admission to intensive care unit with severe sequelae. However, the literature search revealed both for and against studies in this context. Thus, at present, in light of the mixed studies, it cannot be established whether low testosterone levels in aging hypogonadal males create a permissive environment for severe response to coronavirus disease 2019 (COVID-19) infection and can it increase the morbidity or mortality, or on the contrary if the virus inhibits androgen formation. Hence, it is highly warranted to establish the said hypothesis by conducting large statistically powered clinical studies in future. Further, it is highly indicated that impact of sex hormones and gender on the incidence and case fatality of the disease and hormones as a treatment according to sex and gender for COVID requires further scientific research by the research community before it is actually recommended to mitigate the COVID-19 disease course among elderly men and women at large.

Menopause and Sleep Disorders.

Women are likely to suffer from sleep disorders more in comparison to men during menopause and with advancing age. The incidence of sleep disorders ranges from 16% to 47% at peri-menopause and 35%-60% at postmenopause. Insomnia with or without associated anxiety or low lying depression and Mood disorder is most common associated manifestations. Sleep disorders and insomnia largely remain a clinical diagnosis based on the subjective complaints of patients. Benzodiazepines remain the mainstay of the treatment in majority of the sleep disorders including chronic or acute insomnia. Treatment of associated anxiety, depression, or psychosis is most important. Tricyclic antidepressant, Selective Serotonin Reuptake Inhibitors (SSRI), Melatonin, Duloxetine, Fluoxetine, Imipramine, Nortriptyline or Amitriptyline and other drugs such as Eszopiclone, Escitalopram, Gabapentin, Quiteiapine, Citalopram, Mirtazapine followed by long-acting Melatonin and Ramelteon, also are very useful for the management of various sleep disorders. Hormone replacement therapy presently lacks concrete evidence to be used in menopausal women for sleep disorder. Sleep hygiene practices, self-hypnosis, meditation, and exercise play a very important role.

Improvement in Quality of Life of Postmenopausal Women with Depression with commonly used Antidepressants (Escitalopram vs. Desvenlafaxine): A Randomized Controlled Trial in a Tertiary Care Teaching Hospital of North India.

Introduction: The postmenopausal symptoms affect the quality of life (QoL) of women. Depression and anxiety too have been associated with diminished QoL. It is known that antidepressants escitalopram and desvenlafaxine are effective in the treatment of depression and anxiety. However, to the best of our knowledge, their comparative effect on the QoL of postmenopausal women with depression and anxiety has not been studied in the Indian setup. Materials and Methods: The present study was a randomized, intention to treat, open-label trial undertaken in North India's a tertiary care teaching hospital. Postmenopausal women attending the psychiatry outpatient department and newly diagnosed with depression and anxiety were randomized in two groups to receive Tab. Escitalopram 10-20 mg and Tab. Desvenlafaxine 50-100 mg. Their QoL was assessed using the WHOQOL BREF scale at baseline, 3 weeks and 6 weeks. Results: Escitalopram was observed to be statistically better than desvenlafaxine in improving the overall QoL score of the WHOQOL-BREF scale. Individually, escitalopram significantly improved the scores of the physical health domain, psychological and environmental domains except for the social relationship domain. Desvenlafaxine significantly improved scores of all four domains. Conclusion: Escitalopram was observed to be significantly better than desvenlafaxine in improving the overall QoL scores. Both the drugs were well tolerated.

Comparative Efficacy and Safety of Clonazepam versus Nortrptilline on Menopausal Symptom among Forty Plus Women: A Prospective, Open-Label Randomized Study.

AIMS AND OBJECTIVES: The aim of this study is to compare the effect of clonazepam and nortryptiline on menopausal symptoms in above 40 years women. MATERIALS AND METHODS: A prospective, randomized, open-label comparative study was conducted in a tertiary care teaching hospital for 1 year. Patients were randomized into two groups. Both the groups had 60 patients, out of which Group A had 39 menopausal patients and Group B had 31 menopausal patients, respectively. Group 1 received tablet clonazepam 0.5 mg bed time orally daily. Group 2 received tablet nortryptiline 25 mg bed time orally daily. The primary efficacy end points were effect on menopausal symptoms evaluated by at 0, 4, and 8 weeks. RESULTS: Mean age since menopause was 45 ± 4.06 years, and the mean number of years since menopause was 9.18 ± 7.59 years clonazepam and nortryptiline recorded statistically comparable effect with numerical superiority of nortryptiline both at 4 and 8 weeks on mean Menopausal Symptom Score, thereby indicating that both the drugs may have directly/indirectly improved the mean menopausal symptoms equally. Improvement in the clonazepam group was numerically and statistically more than nortryptiline group at 4 and 8 weeks on mean Vasomotor Symptom Score with P < 0.01 in clonazepam group and P < 0.05 in nortryptiline group both at 4 and 8 weeks. Both the drugs showed comparable results on psychosocial symptom score both at 4 and 8 weeks with numerical superiority in nortryptiline group. Clonazepam group showed more improvement on mean physical score than nortryptiline group numerically and statistically. Both the drugs showed comparable results on mean sexual symptom score at 4 weeks, but nortryptiline proved to be statistically better at 8 weeks P < 0.01 versus P < 0.05 in clonazepam group. CONCLUSION: Clonazepam and nortryptiline recorded statistically comparable effect at 4 and 8 weeks on mean menopausal symptom. Both the drugs were equally safe and did not recorded any serious Adverse Drug Reaction (ADRs).

Comparative Efficacy and Safety of Clonazepam versus Nortriptyline in Restless Leg Syndrome among Forty Plus Women: A Prospective, Open-Label Randomized Study.

AIMS AND OBJECTIVES: The aim of this study is to compare the effect of clonazepam and nortriptyline on rate, frequency, and severity of restless leg syndrome (RLS) in above 40 years women suffering from RLS. MATERIALS AND METHODS: A prospective, randomized, open-label comparative study was conducted at a tertiary care teaching hospital for 1 year. Restless legs syndrome (RLS) diagnosis was based on four essential clinical criteria established by the International RLS Study Group in 2003. Patients were randomized into two groups. Group 1 received tablet clonazepam 0.5 mg bedtime orally daily. Group 2 received tablet nortriptyline 25 mg bedtime orally daily. The primary efficacy endpoints by the International Restless leg Syndrome Scale (IRLS) were evaluated at 0, 4, and 8 weeks. Adverse drug events and safety assessment for vital signs such as blood pressure, pulse, heart rate, waist circumference, and body mass index were compared between two groups. RESULTS: Effect on mean IRLSS was statistically more in clonazepam group in comparison to nortriptyline group with comparable results at 8 weeks (P < 0.001), but at 4 weeks, nortriptyline showed less improvement (P < 0.01) versus P < 0.001 in nortriptyline group. Thus, nortriptyline reported relatively more improvement on IRLSS numerically in comparison to clonazepam. Nortriptyline proved to be statistically better in improving the frequency of RLS with comparison to clonazepam, whereas the results were comparable with regard to rate and the severity of RLS. Both the groups were relatively safe and did not produce any change in biochemical parameters and were free from any serious or severe adverse events and overall, both the treatments were well tolerated. CONCLUSION: Both the drugs provided clinically and statistical significant effect on RLS when compared with their respective baselines. However, nortriptyline proved to be statistically better in improving the frequency of RLS in comparison to clonazepam, whereas the results were comparable with regard to rate and the severity of RLS on intergroup comparison. Both the drugs were well tolerated.

Comparative Efficacy and Safety of Escitalopram versus Desvenlafaxine in Postmenopausal Women with Depression and Anxiety: A Randomized, Open-Label, Comparative Trial.

AIMS AND OBJECTIVES: The aim was to evaluate the comparative efficacy and safety of escitalopram versus desvenlafaxine in postmenopausal women with depression and anxiety in our study cohort. MATERIALS AND METHODS: A randomized, open-label, intention-to-treat, comparative study was conducted over a period of 1 year. Group 1 (n = 20) patients received tablet escitalopram 10 mg once daily orally which was increased to 20 mg/day when needed at the first follow-up. Group 2 (n = 20) patients received tablet desvenlafaxine 50 mg once daily orally which was increased to 100 mg/day when needed at the first follow-up. Patients were followed at 3 and 6 weeks. Primary endpoints were change in baseline scores (recorded as mean ± standard deviation) of Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A), and safety was also assessed and compared. RESULTS: Forty patients completed the study. Escitalopram was statistically better than desvenlafaxine in reducing depression after 6 weeks of treatment (P < 0.05). Both the drugs were found to be equally effective in treating anxiety. Furthermore, they showed comparable safety and tolerability. CONCLUSION: Escitalopram appears to be more effective on short-term basis in treating depression, and both the drugs appear equally effective in combating anxiety. Furthermore, they appear to be equally safe and well tolerated in postmenopausal women with depression and anxiety.

A Prospective, Randomized, Open-Label Study Comparing the Efficacy and Safety of Clonazepam versus Nortriptyline on Quality of Life in 40+ Years old Women Presenting with Restless Leg Syndrome.

INTRODUCTION: Restless legs syndrome (RLS) is a neurological disorder characterized by an urge to move the legs usually accompanied by unpleasant leg sensations. RLS also impacts health related quality of life (QOL) in patients suffering from it. Further, it affects women more than men. Although a voluminous literature of studies is available evaluating the role of benzodiazepines (clonazepam and antidepressant (nortriptyline) in the treatment of RLS, but to the best of our knowledge, no comparative study is available comparing both of these drugs for efficacy and safety for the treatment of RLS QoL among 40 + years old women. MATERIALS AND METHODS: A prospective, randomized, open label comparative study was conducted in Postgraduate Department of Pharmacology in collaboration with the Department of General Medicine, Government Medical College, Jammu, a tertiary care teaching hospital for 1 year. CONCLUSION: Clonazepam proved to be significantly better in improving RLSQoL score. Difference between respective baselines of both groups was statistically insignificant.

Digital gangrene induced by inadvertent intra-arterial cocktail injection of anesthetic agents such as pentazocine, promethazine, and atropine: A serious adverse drug experience.

Gangrenous changes in skin due to accidental intra-arterial injection of promethazine and pentazocine have been reported. Accidental intra-arterial injection is most commonly encountered in the antecubital fossa. However, recent reports in the radial and ulnar arteries have also been encountered. We hereby report a serious, preventable adverse drug experience in the form of digital gangrene induced by inadvertent intra-arterial cocktail injection of anesthetic agents such as pentazocine, promethazine, and atropine, which seems to be in the radial artery as the lateral three digits and dorsum of the hand are affected.

Comparative effects of conventional B-blockers and nebivolol on psychomotor performances in healthy volunteers: a preliminary report.

The present study was under taken to assess the comparative effects of nebivolol with propranolol and atenolol on psychomotor performances. Thirty healthy volunteers were randomized into three groups with n=10 in each group. Each subject received single dose of one of the three medications (nebivolol 5 mg, atenolol 50 mg and propranolol 40 mg) in morning (9:00 AM). Just before administering the drug, the pre-drug scores were taken, followed by post drug score obtained for consecutive six hours. Psychomotor assessment was carried out by three tests Simple Reaction Timer (SRT), Critical Flicker Fusion Frequent Threshold (CFFT) and Digit Cancellation Test (DCT). The results of present study indicate that single doses of atenolol and propranolol produced significant impairment of psychomotor performance. Nebivolol also impaired psychomotor performance tests in the similar fashion to atenolol and propranolol. Hence, the findings of the present study correlate with the lipophilic nature of the nebivolol.

Vitex negundo Linn (VN) leaf extract as an adjuvant therapy to standard anti-inflammatory drugs.

BACKGROUND & OBJECTIVES: Leaves of Vitex negundo (VN) have been investigated for their antiinflammatory activity in past, including its mechanism of action. However, nobody has evaluated its potential role as an adjuvant with standard anti-inflammatory therapy. Therefore, the present study was undertaken to investigate interaction of ethanolic leaf extract of VN Linn with standard anti-inflammatory drugs in sub-effective doses per orally (PO) to evaluate its potential role as an adjuvant therapy. METHODS: Carrageenin induced hind paw oedema and cotton pellet granuloma test in albino rats were employed to study interaction of Vitex negundo (VN) leaf extract with standard antiinflammatory drugs in sub-effective doses per orally to evaluate its potential role as an adjuvant therapy. RESULTS: The sub-effective dose of VN potentiated anti-inflammatory activity of phenlbutazone and ibuprofen significantly in carrageenin induced hind paw oedema and cotton pellet granuloma models. INTERPRETATION & CONCLUSION: The potentiation of anti-inflammatory activities phenlbutazone and ibuprofen by VN indicates that it may be useful as an adjuvant therapy along with standard antiinflammatory drugs.

Pregnancy and rheumatoid arthritis.

Pregnancy in most cases, is associated with remission of rheumatoid arthritis (RA), but a quarter of patients continue to have active disease or even worsening of the disease and most patients who improve, relapse in the postpartum period. The pathophysiology of this improvement in disease activity during pregnancy remains unknown, but hormonal, cell-mediated immunological and humoral immunological changes during pregnancy, have been proposed responsible for this. Most of the pregnant women with RA have an uneventful course, with no significant complications. In general, no significant increase in maternal or fetal morbidity seems to be attributable to RA. Patients with RA do not have decreased fertility. A majority of patients with RA may go in remission and anti-rheumatic treatment may not be required as soon as women become pregnant. But other patients who continue with the disease activity require treatment. The preferred disease-modifying agents during pregnancy are sulfasalazine and hydroxychloroquine. Azathioprine and cyclosporine can be used if the benefits outweigh the risks. Paracetamol and low dose prednisone are preferred and considered safe, both for mother and fetus. Methotrexate and lefunomide are contraindicated and must be prophylactically withdrawn before a planned pregnancy. Biologics generally should be stopped when pregnancy is discovered. An overall rational approach is highly warranted to treat RA during pregnancy.

Preliminary screening of osteoporosis and osteopenia in urban women from Jammu using calcaneal QUS.

BACKGROUND: Osteoporosis is a major public health problem, associated with substantial morbidity and socio-economic burden. An early detection can help in reducing the fracture rates and overall socio-economic burden in such patients. AIM: The present study was carried out to screen the bone status (osteopenia and osteoporosis) above the age of 25 years in urban women population in this region. MATERIALS AND METHODS: A hospital based study was carried out in 158 women by calculating T-scores utilizing calcaneal QUS as diagnostic tool. RESULTS: The result suggested that a substantial female population had oesteopenia and osteoporosis after the age of 45 years. The incidence of osteoporosis was (20.25%) and osteopenia (36.79%) with maximum number of both osteoporosis and osteopenic women recorded in the age group of (55-64 years). After the age of 65 years, there was an almost 100% incidence of either osteopenia or osteoporosis, indicating that it increases with age and in postmenopausal period, thereby suggesting lack of estrogenic activity might be responsible for this increasing trend. Religion, caste and diet had an influence on the outcome of osteopenic and osteoporosis score in present study, but still it has to be substantiated by conducting larger randomized clinical trials in future. CONCLUSION: A substantial female population was screened for osteoporosis and osteopenia using calcaneal QUS method utilizing same WHO T score criteria that otherwise shall remain undiagnosed and face the complications and menace of osteoporosis.