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Tricyclic Antidepressants (tricyclic + antidepressants)
Selected AbstractsMania associated with antidepressant treatment: comprehensive meta-analytic reviewACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2010L. Tondo Tondo L, Vázquez G, Baldessarini RJ. Mania associated with antidepressant treatment: comprehensive meta-analytic review. Objective:, To review available data pertaining to risk of mania,hypomania among bipolar (BPD) and major depressive disorder (MDD) patients with vs. without exposure to antidepressant drugs (ADs) and consider effects of mood stabilizers. Method:, Computerized searching yielded 73 reports (109 trials, 114 521 adult patients); 35 were suitable for random effects meta-analysis, and multivariate-regression modeling included all available trials to test for effects of trial design, AD type, and mood-stabilizer use. Results:, The overall risk of mania with/without ADs averaged 12.5%/7.5%. The AD-associated mania was more frequent in BPD than MDD patients, but increased more in MDD cases. Tricyclic antidepressants were riskier than serotonin-reuptake inhibitors (SRIs); data for other types of ADs were inconclusive. Mood stabilizers had minor effects probably confounded by their preferential use in mania-prone patients. Conclusion:, Use of ADs in adults with BPD or MDD was highly prevalent and moderately increased the risk of mania overall, with little protection by mood stabilizers. [source] Treatment of behavioural symptoms and dementia in Parkinson's diseaseFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2005Hasmet A. Hanagasi Abstract Behavioural symptoms such as anxiety, depression and psychosis are common in Parkinson's disease (PD), and dementia occurs in about 90% of the patients. These symptoms can be more disabling than the motor dysfunction and they negatively impact quality of life, increase caregiver distress and are more frequently associated with nursing home placement. Depression can be treated with counselling and pharmacotherapy. Tricyclic antidepressants or selective serotonin reuptake inhibitors are widely used, but there is still need for controlled clinical trials. Management of psychosis in PD is complex and includes elimination of identifiable risk factors, reduction of polypharmacy and administration of atypical neuroleptics, which can alleviate psychotic symptoms without worsening motor functions. Clozapine is the best documented atypical neuroleptic shown to be effective against psychosis in PD patients. Cholinesterase inhibitors may prove additional benefit in psychotic PD patients. Recent evidence from small double-blind and open-label trials suggests that cholinesterase inhibitors may be effective in the treatment of dementia associated with PD. [source] Depression Treatment in Rural California:Preliminary Survey of Nonpsychiatric PhysiciansTHE JOURNAL OF RURAL HEALTH, Issue 4 2002Bernardo Ng M.D. Depressive disorders have been recognized as disabling conditions of public health proportions. However, in areas underserved by mental health professionals, the treatment of depressed patients becomes challenging. Furthermore, patients living in rural areas and communities underserwd by health professionals are at risk for high levels of depressive symptoms and low access to care. Physicians (N = 58)of multiple nonpsychiatric specialties in Imperial County, a rural underserved area in California, were surveyed to ascertain their preferred strategies in the management of depressed patients. More than half (57%) of the respondents preferred to either refer patients to a mental health specialist(p > .01) as the only strategy, or in combination with counseling, prescribing medication, or both. The most commonly reported form of counseling was of a supportive nature. The most commonly prescribed drugs were selective serotonin reuptake inhibitors (in order of frequency: fluoxetine, sertraline, and paroxetine). Tricyclic antidepressants and benzodiazepines were identified as first-line drugs by some pediatricians and surgeons. The results of this study support the need for enhanced postgraduate training in the treatment of depression for nonpsychiatric physicians, and greater exposure of psychiatric residents to rural psychiatry. [source] ,2 -adrenoceptors are critical for antidepressant treatment of neuropathic pain,ANNALS OF NEUROLOGY, Issue 2 2009Ipek Yalcin PharmD Objective Tricyclic antidepressants (TCAs) are one of the first-line pharmacological treatments against neuropathic pain. TCAs increase the extracellular concentrations of noradrenaline and serotonin by blocking the reuptake transporters of these amines. However, the precise downstream mechanism leading to the therapeutic action remains identified. In this work, we evaluated the role of adrenergic receptors (ARs) in the action of TCAs. Methods We used pharmacological and genetic approaches in mice to study the role of ARs in the antiallodynic action of the TCA nortriptyline. Peripheral neuropathy was induced by the insertion of a polyethylene cuff around the main branch of the sciatic nerve. The specific role of ,2 -AR was evaluated by studying ,2 -AR,/, mice. We used von Frey filaments to assess mechanical allodynia. Results The antiallodynic action of nortriptyline was not affected by cotreatment with the ,2 -AR antagonist yohimbine, the ,1 -AR antagonists atenolol or metoprolol, or the ,3 -AR antagonist SR 59230A. On the contrary, the ,-AR antagonists propranolol or sotalol, the ,1/,2 -AR antagonists alprenolol or pindolol, or the specific ,2 -AR antagonist ICI 118,551 blocked the action of nortriptyline. The effect of nortriptyline was also totally absent in ,2 -AR,deficient mice. Interpretation Stimulation of ,2 -AR is necessary for nortriptyline to exert its antiallodynic action against neuropathic pain. These findings provide new insight into the mechanism by which antidepressants alleviate neuropathic pain. Our results also raise the question of a potential incompatibility between ,-blockers that affect ,2 -AR and antidepressant drugs in patients treated for neuropathic pain. Ann Neurol 2009;65:218,225 [source] Antidepressants in the Treatment of Neuropathic PainBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2005Sřren H. Sindrup Tricyclic antidepressants and anticonvulsants have long been the mainstay of treatment of this type of pain. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect. The effect of tricyclic antidepressants in neuropathic pain in man has been demonstrated in numerous randomised, controlled trials, and a few trials have shown that serotonin noradrenaline and selective serotonin reuptake inhibitor antidepressants also relieve neuropathic pain although with lower efficacy. Tricyclic antidepressants will relieve one in every 2,3 patients with peripheral neuropathic pain, serotonin noradrenaline reuptake inhibitors one in every 4,5 and selective serotonin reuptake inhibitors one in every 7 patients. Thus, based on efficacy measures such as numbers needed to treat, tricyclic antidepressants tend to work better than the anticonvulsant gabapentin and treatment options such as tramadol and oxycodone, whereas the serotonin noradrenaline reuptake inhibitor venlafaxine appears to be equally effective with these drugs and selective serotonin reuptake inhibitors apparently have lower efficacy. Head-to-head comparisons between antidepressants and the other analgesics are lacking. Contraindications towards the use of tricyclic antidepressants and low tolerability in general of this drug class , may among the antidepressants , favour the use of the serotonin noradrenaline reuptake inhibitors. A recent study on bupropion, which is a noradrenaline and dopamine uptake inhibitor, indicated a surprisingly high efficacy of this drug in peripheral neuropathic pain. In conclusion, antidepressants represent useful tools in neuropathic pain treatment and must still be considered as first line treatments of neuropathic pain. However, without head-to-head comparisons between antidepressants and other analgesics, it is not possible to provide real evidence-based treatment algorithms for neuropathic pain. [source] Contribution of neuroinflammation in burning mouth syndrome: indications from benzodiazepine useDERMATOLOGIC THERAPY, Issue 2008Fabrizio Guarneri ABSTRACT: Characterized by burning and painful oral sensations in absence of clinically significant mucosal abnormalities, the burning mouth syndrome is, despite numerous researches made, basically idiopathic and, consequently, difficult to treat effectively. Therapy with tricyclic antidepressants and benzodiazepines has been proposed, although the exact pathomechanism is not clear. The objective of this study is to define the possible reasons for the efficacy of benzodiazepines in the treatment of the burning mouth syndrome. Starting from the report of eight cases successfully treated with prazepam, the present authors examined the clinical features and the evidence from literature that support the possibility of a role of neuroinflammation in the pathogenesis of the burning mouth syndrome. Available data suggest that the nervous system could be crucial in the pathogenesis of the syndrome (altered perception of pain, disturbance of neural transmission, increased excitability, negative involvement of trigeminal-vascular system), and the present authors' experience lets them suppose a role for neuroinflammation. This hypothesis could also explain the positive response to benzodiazepines in some patients. The important role of neuroinflammation in dermatologic and oral diseases has been only recently investigated and acknowledged. Further studies on the connection between neuroinflammation and burning mouth syndrome could open interesting perspectives in the understanding and management of this difficult clinical condition. [source] Treatment of varicella-zoster virus and postherpetic neuralgiaDERMATOLOGIC THERAPY, Issue 3 2000Daniel A. Carrasco ABSTRACT: Chickenpox is mostly a disease of childhood; shingles usually affects the elderly, but any age group may be afflicted. Although several proved pharmacologic agents are known to be efficacious in the acute phase of varicella-zoster infections, only three are FDA approved for use in immunocompetent zoster patients and one for the use in primary varicella infections. Ongoing studies with immunocompromised patients are determining whether higher doses of newer oral antivirals will be effective. While a cure for postherpetic neuralgia has not been found, effective treatment to reduce its duration and severity means early implementation of newer antiviral agents. While corticosteroids do not prevent postherpetic neuralgia, they do improve the quality of life when used in combination with acyclovir. Often, symptomatic relief with narcotics, topical anesthetics, and tricyclic antidepressants are necessary. [source] Post-traumatic stress disorder: a review of psychobiology and pharmacotherapyACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2001I. Hageman Objective: To review the literature on the psychobiology and pharmacotherapy of PTSD. Method: Relevant studies were identified by literature searches (Pub-med, web of science) and through reference lists. The search was ended by May 2001. Results: There is evidence of involvement of opioid, glutamatergic, GABAergic, noradrenergic, serotonergic and neuroendocrine pathways in the pathophysiology of PTSD. Medications shown to be effective in double-blind placebo-controlled trials includes selective serotonin reuptake inhibitors, reversible and irreversible MAO-inhibitors, tricyclic antidepressants and the anticonvulsant lamotrigine. Still more agents appear promising in open-label trials. Conclusion: The complexity of the psychobiology is reflected by the difficulties in treating the disorder. According to the present knowledge, suggestions for drug treatment of PTSD are made. [source] EFNS guidelines on pharmacological treatment of neuropathic painEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2006N. Attal Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials. This EFNS Task Force aimed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain. Studies were identified using first the Cochrane Database then Medline. Trials were classified according to the aetiological condition. All class I and II controlled trials (according to EFNS classification of evidence) were assessed, but lower-class studies were considered in conditions that had no top level studies. Only treatments feasible in an outpatient setting were evaluated. Effects on pain symptoms/signs, quality of life and comorbidities were particularly searched for. Most of the randomized controlled trials included patients with postherpetic neuralgia (PHN) and painful polyneuropathies (PPN) mainly caused by diabetes. These trials provide level A evidence for the efficacy of tricyclic antidepressants, gabapentin, pregabalin and opioids, with a large number of class I trials, followed by topical lidocaine (in PHN) and the newer antidepressants venlafaxine and duloxetine (in PPN). A small number of controlled trials were performed in central pain, trigeminal neuralgia, other peripheral neuropathic pain states and multiple-aetiology neuropathic pains. The main peripheral pain conditions respond similarly well to tricyclic antidepressants, gabapentin, and pregabalin, but some conditions, such as HIV-associated polyneuropathy, are more refractory. There are too few studies on central pain, combination therapy, and head-to-head comparison. For future trials, we recommend to assess quality of life and pain symptoms or signs with standardized tools. [source] Antiepileptic Drugs in Migraine PreventionHEADACHE, Issue 2001Ninan T. Mathew MD Migraineurs may continue to experience attacks, despite daily use of one or more agents from a wide range of drugs, including , -blockers, calcium channel blockers, serotonin antagonists, tricyclic antidepressants, monoamine oxidase inhibitors, and antiepileptic agents. Divalproex sodium is the only antiepileptic drug approved for migraine prevention. Gabapentin, topiramate, and other antiepileptic agents are being evaluated for migraine prevention and treatment. Prospective, double-blind, placebo-controlled clinical trials of divalproex, gabapentin, and topiramate for migraine prevention generally were composed of a prospective baseline period, a dose titration period, and a fixed-dose treatment period. The primary efficacy variable was a reduction in the 28-day frequency of migraine headache. Patients receiving divalproex for 12 weeks at doses up to 1500 mg/day achieved significant decreases in the migraine frequency (P<.05), corresponding to reductions of 30% to 40% compared with baseline. Nearly half of the divalproex-treated patients had a 50% or more reduction from baseline in headache frequencies (P.05). Asthenia, vomiting, somnolence, tremor, and alopecia were common adverse events associated with divalproex. Significant reductions in migraine frequency were also observed with gabapentin (1800 to 2400 mg/day) when compared with placebo (P<.01), and nearly half of all patients treated at the highest dose experienced a reduction in headache rate of 50% or more. Somnolence was the most commonly reported adverse event among the gabapentin-treated patients. Two single-center, double-blind, placebo-controlled clinical trials evaluated topiramate for migraine prevention. A lower 28-day migraine frequency was seen during 18 weeks of administration at a maximum daily dose of 200 mg (P = .09). In a second study, a significantly lower mean 28-day migraine frequency was observed during 16 weeks of treatment with topiramate (P = .0015). Mean reduction in migraine frequency was also significantly greater in topiramate-treated patients (P = .0037). Paresthesias, diarrhea, somnolence, and altered taste were commonly reported adverse events in the topiramate-treated patients. Unlike some patients given divalproex or gabapentin, some given topiramate reported weight loss. Large, double-blind, placebo-controlled trials may prove the effectiveness of novel antiepileptic drugs in migraine prevention. [source] Neurological complications of psychiatric drugs: clinical features and management,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2008Peter M. Haddad Abstract This paper reviews the main neurological complications of psychiatric drugs, in particular antipsychotics and antidepressants. Extrapyramidal syndromes include acute dystonia, parkinsonism, akathisia, tardive dyskinesia and tardive dystonia. Extrapyramidal symptoms (EPS) are less frequent with atypical than with conventional antipsychotics but remain common in clinical practice partly due to lack of screening by health professionals. Neuroleptic malignant syndrome (NMS) consists of severe muscle rigidity, pyrexia, change in conscious level and autonomic disturbance but partial forms also occur. NMS is particularly associated with the initiation and rapid increase in dose of high-potency antipsychotics but it has been reported with all the atypical antipsychotics and rarely with other drugs including antidepressants. Serotonin toxicity comprises altered mental state (agitation, excitement, confusion), neuromuscular hyperactivity (tremor, clonus, myoclonus, hyper-reflexia) and autonomic hyperactivity and occurs on a spectrum. Severe cases, termed serotonin syndrome, usually follow the co-prescription of drugs that increase serotonergic transmission by different pathways, for example a monoamine oxidase inhibitor (MAOI) and a selective serotonin reuptake inhibitor (SSRI). Most antipsychotics and antidepressants lower the seizure threshold and can cause seizures; the risk is greater with clozapine than with other atypical antipsychotics and greater with tricyclic antidepressants (TCAs) than with SSRIs. In randomised controlled trials in elderly patients with dementia atypical antipsychotics are associated with a higher risk of stroke and death than placebo. Cohort studies suggest that conventional drugs carry at least the same risk. Cessation of treatment with antipsychotics and antidepressants can lead to a wide range of discontinuation symptoms which include movement disorders and other neurological symptoms. Clinicians need to be familiar with strategies to reduce the risk of these adverse events and to manage them when they arise. Their occurrence needs to be balanced against the benefits of psychiatric drugs in terms of efficacy and improved quality of life in a range of disorders. Copyright © 2007 John Wiley & Sons, Ltd. [source] Pharmacological principles of antidepressant efficacyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2002Alan F. Schatzberg Abstract Both noradrenaline (NA) and serotonin (5-HT) appear to be involved in depression. Evidence suggests that dual-acting antidepressants, i.e. those that affect both monoamine systems, such as tricyclic antidepressants and the noradrenergic and specific serotonergic antidepressant mirtazapine, may have greater efficacy and a faster onset of action than drugs that act on a single monoamine system only, such as the selective serotonin reuptake inhibitors (SSRIs). Cell firing is reduced by SSRIs in the short-term, but is increased by mirtazapine, probably due to its actions on both NA (via ,2 antagonism) and 5-HT (via ,1 -stimulation by NA). This may help to explain clinical evidence suggesting that mirtazapine has a faster onset of action than the more selective antidepressants. Copyright © 2002 John Wiley & Sons, Ltd. [source] An overview of the clinical efficacy of mirtazapineHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2002O. Benkert Abstract Mirtazapine is at least as effective as the tricyclic antidepressants and trazodone in a wide range of patient subgroups including in- and out-patients with moderate to severe depression. It also appears to be at least as effective as the serotonin and noradrenaline reuptake inhibitor venlafaxine in the treatment of severely depressed melancholic patients. When compared with the selective serotonin reuptake inhibitors (SSRIs), mirtazapine shows a significantly earlier onset of action. Further analysis of a study comparing mirtazapine with the SSRI paroxetine indicated that early improvement was a highly sensitive predictor of later stable response for both drugs. The positive predictive value of an early improvement was significantly higher during mirtazapine treatment compared with paroxetine. The negative predictive value approached maximum values as early as week 2 with mirtazapine and week 3 with paroxetine. This suggests that the predictability of the response to treatment is better with mirtazapine than with paroxetine. Copyright © 2002 John Wiley & Sons, Ltd. [source] Tolerability and safety of fluvoxamine and other antidepressantsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2006H. G. M. Westenberg Summary Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) and the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in treatment for depression. The highly specific actions of SSRIs of enhancing serotonergic neurotransmission appears to explain their benefit, while lack of direct actions on other neurotransmitter systems is responsible for their superior safety profile compared with tricyclic antidepressants. Although SSRIs (and venlafaxine) have similar adverse effects, certain differences are emerging. Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern. SSRIs have a cardiovascular safety profile superior to that of tricyclic antidepressants for patients with cardiovascular disease; fluvoxamine is safe in patients with cardiovascular disease and in the elderly. A discontinuation syndrome may develop upon abrupt SSRI cessation. SSRIs are more tolerable than tricyclic antidepressants in overdose, and there is no conclusive evidence to suggest that they are associated with an increased risk of suicide. Although the literature suggests that there are no clinically significant differences in efficacy amongst SSRIs, treatment decisions need to be based on considerations such as patient acceptability, response history and toxicity. [source] Factors associated with antidepressant use in depressed and non-depressed community-dwelling elderly: the three-city studyINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 3 2008Agnčs Soudry Abstract Objectives The aim of this study was to identify factors associated with antidepressant use in non-depressed and depressed elderly persons, assuming that they varied according to clinical status. Methods We studied 7,868 French community-dwelling subjects aged 65 years and over. The Center for Epidemiological Studies-Depression scale and the Mini International Neuropsychiatric Interview were used to define three groups: non-depressed, high depressive symptoms and current major depressive disorder. Separate analyses were performed to identify the factors which were associated with antidepressant use in each group. Results Antidepressant use (55% selective serotonin re-uptake inhibitors, 25% tricyclic antidepressants, 20% other types) increased from 4.9% in non-depressed subjects to 17.3% in subjects with high depressive symptoms (HDS) and 33.6% of in those with current major depressive disorder (MDD). The factors associated with antidepressant use varied according to depression status. In particular, men with current MDD were more often treated with antidepressants than women whereas, in both the HDS and the non-depressed groups, antidepressant use was, as has been observed elsewhere, more frequent in women. Gender also had a strong modifying effect on the relationship between antidepressant use and history of major depression. Finally, the direction of the association between antidepressant use and cognitive performance varied according to depression status. Conclusions This study showed that the direction and strength of the association between antidepressant use and demographic and health-related factors varied according to the severity of depression symptoms. Further studies are needed to clarify the relationship between gender and cognition and antidepressant use. Copyright © 2007 John Wiley & Sons, Ltd. [source] Trends in suicide from drug overdose in the elderly in England and Wales, 1993,1999INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2002Rajen Shah Abstract Background Drug overdose is a common method of suicide in the elderly. Hence, an understanding of current trends in epidemiology of these deaths is important when considering measures to decrease suicide rates. Methods Analysis of the Office for National Statistics (ONS) database of deaths from overdose and poisoning. Suicide and undetermined deaths from drug overdose between 1993,1999 in the over 65 year olds were studied. Socio-demographic data from the four drug groups most commonly used in overdose were extracted, and age and sex specific mortality rates calculated. Enumeration districts were ranked into five quintiles based on their Carstairs scores, and death rates in each quintile for men and women calculated. Results There were 1864 deaths from drug overdose during the study period. Suicide and undetermined death rates from drug overdose remained stable between 1993,1999. Drugs most commonly used in overdose were (in order) paracetamol (and related compounds), benzodiazepines, antidepressants, and opiates. Women comprised 62% of deaths. Death rates increased with age, with highest rates in men over 75 (37.7 deaths per million). Benzodiazepines showed the most marked increase with age. Co-proxamol comprised 32% of deaths from paracetamol compounds, and 95% of antidepressant deaths were due to tricyclic antidepressants. There was no association in women between Carstairs area deprivation and suicide rates; in men rates were highest in the most deprived areas. Conclusion Suicides in the over 65 year olds may be decreased by changes in prescription practice. Paracetamol, co-proxamol, tricyclic antidepressants and benzodiazepines should be prescribed with caution to the elderly with depression or at high risk of depression. Copyright © 2002 John Wiley & Sons, Ltd. [source] Shifts in metabolic parameters surrounding glucose homoeostasis resulting from tricyclic antidepressant therapy: implications of insulin resistance?JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2007W. Chadwick This study displayed the physiological effects the tricyclic antidepressants amitriptyline or trimipramine have on glucose homoeostasis in male Wistar rats. An insulin secreting cell line (INS-1) was also used to determine effects tricyclic antidepressants have on insulin secretion and insulin displacement. Thirty rats each received a 1 mg kg,1 dose of amitriptyline or trimipramine for a period of 14 weeks; another 14 rats served as the control group. Blood glucose, serum insulin and muscle and liver glycogen levels were determined. Kidney, liver and muscle insulin degradation was measured and compared with insulin degrading enzyme concentrations in the latter two tissues. INS-1 cells were used to determine the effect 1,M amitriptyline has on insulin secretion. Displacement studies for [3H]glibenclamide by amitriptyline or trimipramine were undertaken on INS-1 cells. A significant increase in blood glucose (P < 0.01) was found for both test groups after 6 and 14 weeks of receiving the medication, which may be related to a significant decrease in liver and muscle glycogen levels (P < 0.001). Serum insulin levels remained unchanged, although a significant increase in insulin degradation was observed in the muscle, liver and kidney, which may be related to a significant increase in insulin degrading enzyme (P < 0.001) that was found. A significant increase in insulin secretion was observed for the INS-1 cells treated with amitriptyline, although no significant displacement for the [3H]glibenclamide was evident for amitriptyline or trimipramine. The significant alterations in glucose homoeostasis observed, as well as the significant changes associated with insulin secretion and degradation associated with amitriptyline or trimipramine treatment, imply that prolonged use of these medicines may lead to insulin resistance and full blown diabetes. [source] Inhibition and possible induction of rat CYP2D after short- and long-term treatment with antidepressantsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2002Wladys, awa A. Daniel The aim of this study was to investigate the influence of tricyclic antidepressants (imipramine, amitriptyline, clomipramine, desipramine), selective serotonin reuptake inhibitors (SSRIs: fluoxetine, sertraline) and novel antidepressant drugs (mirtazapine, nefazodone) on the activity of CYP2D, measured as a rate of ethylmorphine O -deethylation. The reaction was studied in control liver microsomes in the presence of the antidepressants, as well as in microsomes of rats treated intraperitoneally for one day or two weeks (twice a day) with pharmacological doses of the drugs (imipramine, amitriptyline, clomipramine, nefazodone 10 mg kg,1 i.p.; desipramine, fluoxetine, sertraline 5 mg kg,1 i.p.; mirtazapine 3 mg kg,1 i.p.), in the absence of the antidepressants in-vitro. Antidepressants decreased the activity of the rat CYP2D by competitive inhibition of the enzyme, the potency of their inhibitory effect being as follows: clomipramine (Ki = 14 ,M) > sertraline , fluoxetine (Ki = 17 and 16 ,M, respectively) > imipramine , amitriptyline (Ki = 26 and 25 ,M, respectively) > desipramine (Ki = 44 ,M) > nefazodone (Ki = 55 ,M) > mirtazapine (Ki = 107 ,M). A one-day treatment with antidepressants caused a significant decrease in the CYP2D activity after imipramine, fluoxetine and sertraline. After prolonged administration of antidepressants, the decreased CYP2D activity produced by imipramine, fluoxetine and sertraline was still maintained. Moreover, amitriptyline and nefazodone significantly decreased, while mirtazapine increased the activity of the enzyme. Desipramine and clomipramine did not produce any effect when administered in-vivo. The obtained results indicate three different mechanisms of the antidepressants-CYP2D interaction: firstly, competitive inhibition of CYP2D shown in-vitro, the inhibitory effects of tricyclic antidepressants and SSRIs being stronger than those of novel drugs; secondly, in-vivo inhibition of CYP2D produced by both one-day and chronic treatment with tricyclic antidepressants (except for desipramine and clomipramine) and SSRIs, which suggests inactivation of the enzyme apoprotein by reactive metabolites; and thirdly, in-vivo inhibition by nefazodone and induction by mirtazapine of CYP2D produced only by chronic treatment with the drugs, which suggests their influence on the enzyme regulation. [source] Policy on Acute Toxic Ingestion or Dermal or Inhalation ExposureJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 7 2003ANP-C FAANP, Mary Jo Goolsby EdD ABSTRACT Many nurse practitioners (NPs) practice in emergency and urgent-care settings, and fir more practical remote settings. NPs in each of these settings should be familiar with the assessment, stabilization, and treatment of patients who seek treatment for suspected intentional or accidental poisoning. This month's Clinical practice guideline (CPG) column reviews the "Clinical Policy for the Initial Approach to Patients Presenting With Acute Toxic Ingestion or Dermal or Inhalation Exposure." SUMMARY The ACEP "Clinical Policy for the Initial Approach to Patients Presenting With Acute Toxic Ingestion or Dermal or Inhalation Exposure" includes several helpful resources. In addition to recommending specific clinical actions in response to patient variables, the document includes a table identifying the antidote for many of the most commonly ingested drugs. These include digoxin, iron, opioids, salicylates, acetaminophen, and tricyclic antidepressants. The table also includes both the adult and pediatric dose of each listed antidote. A quick reference is included. This form can be used to guide the history, physical examination, and subsequent actions for treating patients with acute toxic ingestion or dermal or inhalation exposure. Finally, there is a quality assurance form to guide chart reviews. Many of the attributes of a well-developed guideline are identified in the report. The authors clearly identify the situations for which the recommendations are intended as well as those in which they do not apply. For instance, the guidance is not intended for use when patients are unstable and stabilization is the primary focus. It is also not intended for cases of radiation, parenteral, or eye exposure or of food poisoning. The authors describe the process used to develop the recommendations and identify the strength of the evidence on which each recommendation is based. The role of provider judgment in application of the guidance is addressed. Prior to its dissemination, the CPG was subjected to external review by dinical experts. This ACEP policy has applicability for the growing number of NPs working in emergency and urgent cafe settings as well as for those who must provide front line emergency care in remote settings. It provides a framework for responding to acute toxic exposures and provides several useful resources to assist the clinician in responding to situations in which accidental or intentional poisoning is suspected. [source] Depression and treatment with antidepressants are associated with the development of gastro-oesophageal reflux diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2010E. MARTÍN-MERINO Aliment Pharmacol Ther,31, 1132,1140 Summary Background, The roles of depression and antidepressants in triggering reflux symptoms remain unclear. Aim, To compare the incidence of gastro-oesophageal reflux disease (GERD) in individuals with and without a depression diagnosis and to evaluate risk factors for a GERD diagnosis. The relationship between antidepressant treatment and GERD was also assessed. Methods, The Health Improvement Network UK primary care database was used to identify patients with incident depression and an age- and sex-matched control cohort with no depression diagnosis. Incident GERD diagnoses were identified during a mean follow-up of 3.3 years. Furthermore, we performed nested case-control analyses where odds ratios (OR) with 95% confidence intervals (CI) were estimated by unconditional logistic regression in multivariable models. Results, The incidence of GERD was 14.2 per 1000 person-years in the depression cohort and 8.3 per 1000 person-years in the control cohort. The hazard ratio of GERD in patients with depression compared with controls was 1.72 (95% CI: 1.60,1.85). Among patients with depression, tricyclic antidepressant use was associated with an increased risk of GERD (OR: 1.71; 95% CI: 1.34,2.20), while selective serotonin reuptake inhibitors were not associated with GERD. Conclusions, A depression diagnosis is associated with an increased risk of a subsequent GERD diagnosis, particularly in individuals using tricyclic antidepressants. [source] Major depression: emerging therapeuticsMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2008Srijan Sen MD Abstract The first effective antidepressants, monoamine oxidase inhibitors and tricyclic antidepressants, were identified 50 years ago, largely through serendipity. These medications were found to improve mood in a little more than half of depressed patients after a few weeks of chronic use. Almost all antidepressants prescribed today were developed through minor modifications of these original antidepressants and, like monoamine oxidase inhibitors and tricyclic antidepressants, act primarily through monoaminergic mechanisms. Although there have been improvements in side-effect profiles and overdose toxicity, these newer medications have not provided substantial advances in the efficacy and speed of the antidepressant effect for patients. Over the last 2 decades, our understanding of the neurobiology underlying depression has expanded exponentially. Given this expansion, we may be nearing an inflection point in antidepressant drug development, at which useful medicines will be designed through a rational understanding of the biological systems. In this review, we discuss the biological basis and preclinical and clinical evidence for a series of promising classes of antidepressants developed primarily out of a pathophysiologically informed approach. Mt Sinai J Med 75:203,224, 2008. © 2008 Mount Sinai School of Medicine [source] Clinical and Economic Characteristics of Patients with Painful Neuropathic Disorders in GermanyPAIN PRACTICE, Issue 1 2009Ariel Berger MPH Abstract Using a large database with information from general practitioners (GP) throughout Germany, we identified all adults (age ,18 years) with encounters for painful neuropathic disorders (PNDs) between August 1, 2005 and July 31, 2006 (PND patients). We also constituted an age- and sex-matched comparison group, consisting of randomly selected patients without any GP encounters for PNDs during the same period. Selected characteristics were then compared between PND patients and those in the comparison group over the 1-year study period. The study sample consisted of 275,685 PND patients and a similar number in the matched comparison group; mean age was 53.7 years, and 57% were women. PND patients were more likely than matched comparators to have encounters for various comorbidities, including circulatory system disorders (47% vs. 20%, respectively), depression (9% vs. 2%), and anxiety (4% vs. 1%) (all P < 0.01). They also were more likely to have received pain-related medications (57% vs. 13% for comparison group; P < 0.01),most commonly, nonsteroidal anti-inflammatory drugs, benzodiazepines, and opioids, and less often, tricyclic antidepressants and anti-epileptics. PND patients averaged 7.3 more GP visits during the year (mean [95% CI] = 9.9 [9.9, 9.9] vs. 2.6 [2.6, 2.7] for comparison group); they also had significantly more specialist referrals and physician-excused absences from work (all P < 0.01). Patients with PNDs under the care of GPs in Germany have comparatively more comorbidities and higher levels of use of healthcare services. The pain-related medications that these patients receive raise concerns that PNDs may not be optimally treated in these settings. [source] Neurophatic Pain Treatment: The ChallengePAIN PRACTICE, Issue 1 2003Jose De Andrés Abstract: Neuropathic pain covers a heterogeneous group of pain conditions characterized by a primary lesion or dysfunction of the sensory nervous system. Its pathophysiology is not yet clear, but neuronal hyperexcitability in those neurons that have lost their normal patterned input seems to be a common denominator for neuropathic pain. A mechanism-based approach is being developed, but still the clinical workup is being based on the anatomical location and the determination of an underlying cause. In addition, clinicians are presented with a challenge because neuropathic pain does not respond well to traditional pain therapies and there are greater individual variations in pain responsiveness. A number of drug classes have been evaluated in the treatment of neuropathic pain syndromes; these are mainly drugs developed for other nervous system diseases, although their precise action and whether their action is central or peripheral remains unknown for the majority of them. First-line agents used in the treatment of neuropathic pain conditions are tricyclic antidepressants and anticonvulsants, especially carbamazepine and gabapentin. Novel therapies are currently being developed for neuropathic pain that are based in experimental models and theoretical frameworks on the pathosphysiological events that initiate this type of pain. [source] Herpes zoster in older adults. (Duke University Medical Center, Durham, NC) Clinical Infectious Diseases.PAIN PRACTICE, Issue 4 20011486., 2001;32:148 Herpes zoster (HZ) strikes millions of older adults annually worldwide and disables a substantial number of them via postherpetic neuralgia (PHN). Key aged-related clinical, epidemiological, and treatment features of zoster and PHN are reviewed in this article. HZ is caused by renewed replication and spread of the varicella-zoster virus (VZV) in sensory ganglia and afferent peripheral nerves in the setting of age-related, disease-related, and drug-related decline in cellular immunity to VZV. VZV-induced neuronal destruction and inflammation causes the principal problems of pain, interference with activities in daily living, and reduced quality of life in elderly patients. Recently, attempts to reduce or eliminate HZ pain have been bolstered by the findings of clinical trials that antiviral agents and corticosteroids are effective treatment for HZ and that tricyclic antidepressants, topical lidocaine, gabapentin, and opiates are effective treatment for PHN. Although these advances have helped, PHN remains a difficult condition to prevent and treat in many elderly patients. Comment by Miles Day, M.D. This article reviews the epidemiology clinical features diagnosis and treatment of acute herpes zoster. It also describes the treatment of postherpetic neuralgia. While this is a good review for the primary care physician, the discussion for the treatment for both acute herpes zoster and postherpetic neuralgia do not mention invasive therapy. It is well documented in pain literature that sympathetic blocks with local anesthetic and steroid as well as subcutaneous infiltration of active zoster lesions not only facilitate the healing of acute herpes zoster but also prevents or helps decrease the incidence of postherpetic neuralgia. All patients who present to the primary care physician with acute herpes zoster should have an immediate referral to a pain management physician for invasive therapy. The treatment of postherpetic neuralgia is a challenging experience both for the patient and the physician. While the treatments that have been discussed in this article are important, other treatments are also available. Regional nerve blocks including intercostal nerve blocks, root sleeve injections, and sympathetic blocks have been used in the past to treat postherpetic neuralgia. If these blocks are helpful, one can proceed with doing crynourlysis of the affected nerves or also radio-frequency lesioning. Spinal cord stimulation has also been used for those patients who are refractory to noninvasive and invasive therapy. While intrathecal methylprednisolone was shown to be effective in the study quoted in this article one must be cautious not to do multiple intrathecal steroid injections in these patients. Multilple intrathecal steroid injections can lead to archnoiditis secondary to the accumulation of the steroid on the nerve roots and in turn causing worsening pain. [source] National trend of antidepressant consumption and its impact on suicide rate in Hungary,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2008Réka Viola MSc Pharm Abstract Purpose The aim of this study was to analyse the changes in the amount and structure of Hungarian antidepressant consumption at national and regional level, furthermore to investigate the possible relationship between antidepressant sales and trends in suicide rates using regional data. Method Retrospective analysis of antidepressant sales data was performed on a 12 years period (1993,2004), applying the ATC/DDD methodology developed by WHO. Linear regression model was set up to investigate the trends in antidepressant utilisation. The association between antidepressant consumption and suicide rates was measured by Pearson correlation. Results The nationwide utilisation of antidepressants revealed more than five-fold increase in the studied 12 year period. The usage of tricyclic antidepressants (N06AA) decreased to one third of the previous value, while the usage of selective serotonin reuptake inhibitors (N06AB) multiplied by 21. The consumption of ,other antidepressants' (N06AX) was found very low (3.66 DDD/1000inhabitants/day in 2004). There was not found any significant correlation between increased antidepressant consumption and decreased suicide rates at regional level by our statistical analysis (rmin,=,,0.160; rmax,=,,0.314). Conclusion Further investigation is required to identify determinants that have contributed to recent decline in suicide rate in Hungary. Copyright © 2008 John Wiley & Sons, Ltd. [source] Risk of breast cancer in association with exposure to two different groups of tricyclic antidepressants,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 10 2006Hani Tamim PhD Abstract Purpose In 2002, we reported an epidemiological study in which we found that some tricyclic antidepressants (identified as genotoxic in Drosophila Melanogaster) were associated with an increased risk of breast cancer, when exposure took place 11,15 years before the date of diagnosis. The implications of the results found lead us to carry out a separate case-control study, using the same source population, to validate the conclusions drawn from our previous study. Methods We accrued 7330 breast cancer cases, diagnosed between 1981 and 2000, and 29,320 controls matched on age and time. Results The association between exposure to genotoxic TCAs 11,15 years before diagnosis and the risk of breast cancer development was much weaker, as compared to what was reported in our previous study. The relative risk of breast cancer in women exposed to high doses of genotoxic TCAs 11,15 years before diagnosis was 1.17 (95%CI: 0.79,1.74), while in women exposed to high levels of non-genotoxic TCAs during the same period it was 0.95 (95%CI: 0.61,1.48). Conclusion In conclusion, we did not find supporting evidence for an increased risk of breast cancer among women exposed to TCAs up to 20 years in the past. Copyright © 2006 John Wiley & Sons, Ltd. [source] No predictors of antidepressant patient response to milnacipran were obtained using the three-factor structures of the Montgomery and Ĺsberg Depression Rating Scale in Japanese patients with major depressive disordersPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 2 2008Hisashi Higuchi md Aims:, Milnacipran, a new specific serotonin and norepinephrine re-uptake inhibitor, is as effective as tricyclic antidepressants. Symptomatological predictors of antidepressant response to milnacipran have not been studied until now. Methods:, This study included 101 Japanese patients who fulfilled the DSM-IV criteria for the diagnosis of major depressive disorders and whose score on the Montgomery and Ĺsberg Depression Rating Scale (MADRS) was ,21. Eighty-three patients were finally included. Patients with a pretreatment MADRS score ,31 points were defined as severe (n = 28), and the rest as non-severe (n = 55). The three-factor model of MADRS was used for analysis; the first factor was defined by three items, the second factor was defined by four items and the third factor was defined by three items representing dysphoria, retardation, and vegetative symptoms, respectively. Milnacipran was administered twice daily for 6 weeks. The initial dose was 50 mg/day; after a week it was increased to 100 mg/day. Results:, No significant difference was observed in the mean score of first factor, second factor and third factor at pretreatment time between responders and non-responders in both severe and non-severe patients. Conclusions:, No predictor of antidepressant response to milnacipran was obtained using the three-factor structures of the MADRS in Japanese patients with major depressive disorders. [source] Annotation: The use of psychotropic medications in children: an American viewTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 2 2003Mark L. Wolraich Background: Psychotropic medications have become an integral component in the treatment of children with mental illnesses. Methods: Selective reviews of the empirical evidence for the efficacy of psychotropic medications and studies of their use patterns were reviewed. Results: Very strong efficacy for at least the short-term benefits and safety of stimulant medications was found and some good efficacy and safety evidence for the treatment of anxiety and depressive disorders with seratonin reuptake inhibitors (SSRI) was also found. Efficacy for tricyclic antidepressants to treat attention deficit hyperactivity disorder was found but the presence of significant side effects makes them less the drugs of choice. Other medications are presented but with less rigorous evidence. Studies of use found that stimulant medications are extensively prescribed in the US by both psychiatrists and primary care physicians. SSRI are also prescribed extensively but not to the extent of stimulants and are more frequently prescribed by psychiatrists. Conclusions: There is now good evidence for the efficacy of some psychotropic agents and their use is an integral component in the management of childhood mental illnesses. [source] Novel two-stage screening procedure leads to the identification of a new class of transfection enhancersTHE JOURNAL OF GENE MEDICINE, Issue 6 2006Birgit Neukamm Abstract Background Non-viral gene transfer efficiency is low as compared to viral vector systems. Here we describe the discovery of new drugs that are capable of enhancing non-viral gene transfer into mammalian cells using a novel two-stage screening procedure. Methods First, potential candidates are preselected from a molecular library at various concentrations by a semi-automated yeast transfection screen (YTS). The maximal transfection efficiency of every positive drug is subsequently determined in independent experiments at the optimal concentration and compared to the inhibitory effect of the drug on cell growth (IC50). In a subsequent mammalian cell transfection screen (MTS), the maximal transfection efficiency and the IC50 are determined for all preselected drugs using a human cell line and a luciferase reporter gene construct. Results Employing our novel system we have been able to identify a new class of transfection enhancers, the tricyclic antidepressants (i.e. doxepin, maprotiline, desipramine and amoxapine). All positive drugs enhanced gene transfer in both yeast and human cell lines, but lower concentrations were sufficient for mammalian cells. With a triple combination of doxepin, amoxapine and chloroquine we obtained a transfection efficiency that exceeded that of chloroquine, one of the best-known transfection enhancers of mammalian cells, by nearly one order of magnitude. Conclusions Non-viral gene transfer efficiency can be increased significantly using new transfection enhancers that are identified by a novel, semi-automated two-stage screening system employing yeast cells in the first and specific human target cells in the second round. Copyright © 2006 John Wiley & Sons, Ltd. [source] A real reason for patients with pseudobulbar affect to smileANNALS OF NEUROLOGY, Issue 2 2007Howard J. Rosen MD Pseudobulbar affect (PBA) is a dramatic disorder of emotional expression and regulation characterized by uncontrollable episodes of laughing and crying that often cause embarrassment, curtailment of social activities, and reduction in quality of life. The disorder occurs in patients with brain injury caused by many types of neurological disease, including stroke, tumors, and neurodegenerative gray and white matter disorders. Although the pathophysiology is unknown, PBA may relate to release of brainstem emotional control centers from regulation by the frontal lobes. Diagnosis of PBA can be difficult and relies on careful characterization of episodes and differentiation from depression. Although there are no US Food and Drug Administration,approved treatments for PBA, several agents have been shown to be effective, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and a new agent containing dextromethorphan and quinidine. The growing number of treatment options, some of great benefit to patients, highlights the importance of accurate diagnosis of this disorder. Ann Neurol 2007 [source] | |||||||||||||||||||||||||||||||