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Biomedical subjects

P Benfield

Publications and source records attributed to P Benfield.

At least 55 records · Page 3Linked to original sources
PubMed1993

Zidovudine: a review of pharmacoeconomic and quality-of-life considerations for its use in patients with human immunodeficiency virus.

In patients with human immunodeficiency virus (HIV) infections or the acquired immunodeficiency syndrome (AIDS), zidovudine is a first-line therapy that reduces morbidity and may reduce mortality. By delaying progression to AIDS, the drug reduces the duration and incidence of hospitalisations in a given time period, resulting in overall decreases in the cost of medical treatment per unit of survival time. In current therapeutic dosages zidovudine is generally well tolerated. Most pharmacoeconomic and quality-of-life studies of this agent were conducted using data relating to higher dosages and higher drug acquisition costs than those currently applicable, but nevertheless generally support the cost-effectiveness of zidovudine in patients with HIV disease. Studies examining the use of the drug in higher dosages demonstrate neither clear positive nor negative effects of the drug on quality of life. The cost effectiveness of the drug as prophylaxis against seroconversion after occupational exposure to HIV is dependent primarily on the establishment of clinical effectiveness in this condition. Further pharmacoeconomic studies should examine changes to dosage and cost factors, along with direct nonmedical treatment costs, indirect medical treatment costs and the effects of the drug on quality of life. An evaluation of existing studies suggests that if these factors were accounted for, zidovudine might be shown to be more clearly cost effective, and indeed its use in the treatment of patients with HIV disease might be found to result in cost savings.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Clozapine: an appraisal of its pharmacoeconomic benefits in the treatment of schizophrenia.

Clozapine, an antipsychotic agent with relatively weak central antidopaminergic activity, displays atypical pharmacological and clinical properties vis-a-vis the classic antipsychotics. Thus, clozapine is effective against both the positive and negative symptoms of schizophrenia and has a low propensity to cause extrapyramidal effects. Furthermore, clozapine is effective in a substantial proportion (up to 60%) of patients who are refractory to or intolerant of standard antipsychotic therapy. Despite its promising therapeutic potential, the relatively high incidence of clozapine-induced agranulocytosis (approximately 1% of patients) and the associated need for regular haematological monitoring currently restricts the drug's use to the treatment of chronic and severe schizophrenia refractory to standard antipsychotic therapy, and to those patients unable to tolerate such therapy. In the US, the current wholesale price of clozapine (exclusive of monitoring) is $US2.85 per 100mg tablet, amounting to $US4160 annually (1992 dollars) at the most commonly prescribed dose of 400 mg/day ($US2.40 per tablet and $US3510 annually to state programmes through Medicaid reimbursement legislation). In the UK, the annual cost of clozapine (at the average dose of 300 mg/day), inclusive of blood monitoring, is 1806 British pounds sterling (1992 pounds). Although the acquisition cost of clozapine is high in comparison with that of standard antipsychotics, preliminary cost-effectiveness estimates in patients with treatment-resistant schizophrenia suggest that the clinical benefits of the drug (viz. improved psychopathology, social functioning and quality of life) may confer medium to long term economic benefits, primarily by reducing the need for psychiatric hospital services. This effect is most likely to be seen on long term ( greater than or equal to 2 years) maintenance therapy with clozapine. Savings in hospital costs are, however, likely to be offset, at least initially, by increased reliance on outpatient services, and clozapine may therefore confer additional economic costs during the first year or so of treatment. In the longer term, however, the initial cost investment may be recouped in the form of savings to psychiatric institutions and insurers.

Clozapine↗
PubMed1992

Angiotensin II receptors and functional correlates.

Angiotensin II (ANG II) is the primary mediator of the renin-angiotensin system, which has an important functional role in cardiovascular homeostasis. The angiotensin receptor and its functional correlates have been redefined by the cloning of angiotensin receptors and the discovery and widespread study of specific nonpeptide ANG II-receptor antagonists losartan (AT1 selective) and PD123177 (AT2 selective). With these antagonists, it has been possible to extend the concept of ANG II-receptor heterogeneity to virtually every tissue and species. The losartan-sensitive sites have been shown to mediate all of the major ANG II-induced biologic effects, including vasoconstriction, aldosterone and catecholamine release, and central, ANG II-induced drinking behavior. The function of the AT2 site is not fully understood, but it may be involved in neuronal ion channel modulation and in fibroblast collagen metabolism. The presence of AT2 sites in fetal tissues and in discrete locations in the brain has encouraged continued research. Losartan, which represents the first of a new class of therapeutic agents, is currently undergoing clinical trials. A growing number of other AT1-selective ANG II-receptor antagonists are under development, including L-158,809, SKF 108566, and GR117285. Rat AT1-receptor subtypes have been cloned and sequenced (AT1A and AT1B). Human ANG II receptors have also been cloned and shown to have high affinity for losartan. A number of atypical angiotensin-binding sites have been identified from mycoplasma, amphibians, and mouse neuroblastoma, which are not sensitive to either losartan or PD123177.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylates↗
PubMed1992

Rat brain creatine kinase messenger RNA levels are high in primary cultures of brain astrocytes and oligodendrocytes and low in neurons.

Rat brain creatine kinase (CKB) gene expression is highest in the brain but is also detectable at lower levels in some other tissues. In the brain, the CKB enzyme is thought to be involved in the regeneration of ATP necessary for transport of ions and neurotransmitters. To understand the molecular events that lead to high CKB expression in the brain, we have determined the steady-state levels of CKB mRNA in homogeneous cultures of primary rat brain astrocytes, oligodendrocytes, and neurons. Northern blot analysis showed that whereas the 1.4-kb CKB mRNA was detectable in neurons, the level was about 17-fold higher in oligodendrocytes and 15-fold higher in astrocytes. The blots were hybridized with a CKB-specific 32P-antisense RNA probe, complementary to the 3' untranslated sequence of CKB, which hybridizes to CKB mRNA but not CKM mRNA. Also, the 5' and 3' ends of CKB mRNA from the glial cells were mapped, using exon-specific antisense probes in the RNase-protection assay, and were found to be the same in astrocytes and oligodendrocytes. This indicated that (a) the site of in vivo transcription initiation in astrocytes and oligodendrocytes was directed exclusively by the downstream, nonconcensus TTAA sequence at -25 bp in the CKB promoter that is also utilized by all other cell types that express CKB and (b) the 3' end of mature CKB mRNA was the same in astrocytes and oligodendrocytes. In addition, there was no detectable alternate splicing in exon 1, 2, or 8 of CKB mRNA in rat astrocytes and oligodendrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Imipenem/cilastatin: a pharmacoeconomic appraisal of its use in intra-abdominal infections.

Imipenem/cilastatin possesses a very broad spectrum of antibacterial activity that encompasses the range of Gram-negative and Gram-positive aerobes and anaerobes usually associated with intra-abdominal and other polymicrobial infections. Its therapeutic efficacy is comparable to that of aminoglycoside/antianaerobe combination regimens, and the most commonly reported adverse effects are similar to those of other beta-lactam antibacterials and are generally of a non-serious nature. The acquisition cost of imipenem/cilastatin is generally greater than that of aminoglycoside/antianaerobe combination regimens, but treatment with the latter incurs the additional costs of multiple intravenous administration, aminoglycoside pharmacokinetic and other monitoring, and possible nephrotoxicity and ototoxicity. The available pharmacoeconomic studies show a trend towards lower total treatment costs with imipenem/cilastatin compared with gentamicin plus clindamycin. Results from other sources suggest that imipenem/cilastatin may achieve further cost savings through reduced duration of hospitalisation. Although further study is required to confirm these trends, it appears that the total treatment cost of imipenem/cilastatin does not exceed that of usual combination therapy and the risk of aminoglycoside-induced toxicity is avoided.

Abdomen↗
PubMed1990

Ramipril. A review of its pharmacological properties and therapeutic efficacy in cardiovascular disorders.

Ramipril is a long acting angiotensin converting enzyme (ACE) inhibitor, which exhibits similar pharmacodynamic properties to captopril and enalapril. Like enalapril it is a prodrug, which is hydrolysed after absorption to form the active metabolite ramiprilat which has a long elimination half-life, permitting once daily administration. In hypertensive patients daily doses in the range 2.5 to 20 mg are usually effective in reducing high blood pressure and maintaining satisfactory control during long term treatment. Patients who do not respond adequately to monotherapy with ramipril usually respond with the addition of a diuretic such as hydrochlorothiazide or piretanide. Ramipril 5 to 10 mg once daily shows comparable antihypertensive efficacy to usual therapeutic dosages of captopril, enalapril and atenolol in patients with mild to moderate essential hypertension. Preliminary data indicate that ramipril may be effective in indications such as severe essential hypertension and renal hypertension. It has also displayed beneficial effects in patients with moderate to severe congestive heart failure. Ramipril has been well tolerated and exhibits an adverse effect profile typical of ACE inhibitors as a class. In conclusion, ramipril will likely represent a useful alternative ACE inhibitor for use in patients with hypertension or congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Clomipramine. An overview of its pharmacological properties and a review of its therapeutic use in obsessive compulsive disorder and panic disorder.

During the 20 years that have elapsed since clomipramine (chlorimipramine) was first marketed, it has become well established in the treatment of depressive illness, particularly treatment-resistant depression. However, in addition to its role as an antidepressant, attention is being focused on the use of clomipramine in 2 other areas of psychiatry: obsessive compulsive disorder and panic disorder. Short term clinical trials have shown that clomipramine is generally more effective than amitriptyline, imipramine, desipramine, nortriptyline or clorgiline in reducing obsessive compulsive symptoms. Clomipramine appears to produce some short term benefit with exposure therapy in patients with obsessive compulsive disorder. However, the efficacy of the drug after long term follow-up has not been fully investigated. The antiobsessional efficacy of clomipramine appears to be independent of its antidepressant activity. In patients with panic disorder with or without agoraphobia (DSM-IIIR), clomipramine reduces the frequency and severity of panic attacks within 7 to 21 days of beginning treatment and efficacy is maintained for at least 12 months. Clomipramine is more effective than imipramine, the generally accepted standard treatment for patients with panic disorder after 2 weeks' treatment, but after 6 or 10 weeks both drugs are similarly effective. Other double-blind studies have shown that clomipramine is more effective than placebo and at least as effective as fluvoxamine and oxitriptan (5-hydroxytryptophan) in reducing panic attacks and associated anxiety. Adverse effects associated with clomipramine treatment are mild to moderate in nature and are predominantly a result of the drug's anticholinergic activity. The incidence of seizures is dose related, occurring in 0.48% of all patients receiving clomipramine less than or equal to 250 mg/day and 2.1% of patients receiving greater than or equal to 300 mg/day. In conclusion, the available data indicate that clomipramine is a worthwhile addition to the limited treatments available for obsessive compulsive disorder and panic disorder, two psychiatric disorders which have previously been difficult to manage pharmacologically.

Animals↗
PubMed1990

Amoxicillin/clavulanic acid. An update of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Clavulanic acid enhances the antibacterial spectrum of amoxicillin by rendering most beta-lactamase-producing isolates susceptible to the drug. In clinical trials amoxicillin/clavulanic acid is clinically and bacteriologically superior to amoxicillin alone and at least as effective as numerous other comparative agents, such as orally administered cephalosporins, cotrimoxazole, doxycycline and bacampicillin, in the treatment of adults and children with the most common forms of infection encountered in general practice, i.e. urinary tract infections, upper and lower respiratory tract infections, otorhinolaryngological infections, and skin and soft tissue infections. It may also provide effective treatment for uncomplicated gonorrhoea, chancroid and gynaecological infections as well as acting as a prophylactic agent against surgical infection. Thus, in general practice environments where beta-lactamase production has restricted the effectiveness of amoxicillin, the combination of clavulanic acid with amoxicillin has clearly extended the usefulness of a tried and proven first-line antibacterial agent.

Amoxicillin↗
PubMed1990

Dopexamine hydrochloride. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in acute cardiac insufficiency.

Dopexamine hydrochloride is a novel synthetic catecholamine, structurally related to dopamine, with marked intrinsic agonist activity at beta 2-adrenoceptors, lesser agonist activity at dopamine DA1- and DA2-receptors and beta 1-adrenoceptors, and an inhibitory action on the neuronal catecholamine uptake mechanism. The drug is administered by intravenous infusion, and is characterized by a rapid onset and short duration of action. Short term haemodynamic studies in volunteers and patients with severe chronic heart failure have indicated that dopexamine hydrochloride reduces afterload through pronounced arterial vasodilatation, increases renal perfusion by selective renal vasodilation and evokes mild cardiac stimulation through direct and indirect positive inotropism. Preliminary small-scale noncomparative studies indicate that dopexamine hydrochloride displays beneficial haemodynamic effects in patients with acute heart failure and those requiring haemodynamic support following cardiac surgery, and that these effects are substantially maintained during longer term administration (less than or equal to 24 hours). Dopexamine hydrochloride appears to be generally well tolerated. Nausea and vomiting are the most frequently reported adverse effects, and respond to dosage reduction. Occasional reports of chest pain/angina pectoris precipitated by tachycardia indicates the need for caution in the use of dopexamine hydrochloride in patients with ischaemic heart disease. Thus, dopexamine hydrochloride may prove to be a useful alternative to dopamine and dobutamine in the treatment of acute heart failure and the postoperative management of low cardiac output states, although controlled studies are required to establish its efficacy and tolerability with respect to that of established therapies.

Adrenergic Agonists↗
PubMed1990

Inhaled pentamidine. An overview of its pharmacological properties and a review of its therapeutic use in Pneumocystis carinii pneumonia.

Pentamidine is an aromatic diamidine derivative which has become one of the standard therapies for Pneumocystis carinii pneumonia (PCP), particularly in patients with acquired immunodeficiency syndrome (AIDS). However, with parenteral administration of the drug there is a high risk of toxicity. Inhaled pentamidine produces much higher concentrations of drug on the bronchoalveolar surface with minimal systemic absorption. It has been used successfully for the treatment of PCP in AIDS patients, but its most valuable contribution has been as prophylaxis in AIDS patients at high risk of developing PCP. In prospective controlled studies there has been greater than 80% reduction in relapse rate with pentamidine. The reduction in relapse rate among patients who have experienced one previous episode of PCP has been 50 to 100% compared with historical control groups, over a follow-up period averaging about 6 months. Significant systemic adverse effects to inhaled pentamidine are rare. Respiratory effects associated with inhalation are common but usually controllable without treatment discontinuation. The ideal particle size for even distribution of pentamidine throughout the lung is considered to be 1 to 2 microns. Jet nebulisers such as the 'Respirgard II' system produce a mass median aerodynamic diameter (MMAD) of particles in this range. Ultrasonic nebulisers produce larger particles. The implication from this difference is that while ultrasonic nebulisers may have poorer alveolar distribution and the incidence of local side effects (common with all formulations) may be higher, total drug delivery may be more efficient allowing effective PCP prophylaxis with lower dosages (120 mg vs 300 mg monthly). However, there are no data available comparing the efficacies and tolerabilities of the different formulations of inhaled pentamidine. Nevertheless, inhaled pentamidine would seem poised to become routine prophylaxis in patients with AIDS or AIDS-related complex at risk of developing PCP.

Administration, Inhalation↗
PubMed1990

Guar gum. A review of its pharmacological properties, and use as a dietary adjunct in hypercholesterolaemia.

Guar gum is a dietary fibre advocated for use in lowering serum total cholesterol levels in patients with hypercholesterolaemia. Its mechanism of action is proposed to be similar to that of the bile-sequestering resins. Although guar gum is also employed as an adjunct in non-insulin-dependent diabetic patients this review is restricted to its efficacy as a hypolipidaemic agent. Clinical trials indicate that, when used alone, guar gum may reduce serum total cholesterol by 10 to 15%, although some studies show no significant response. An attenuation of this effect during longer term treatment has been seen but evidence of this effect is equivocal. As an adjunct to established therapies (bezafibrate, lovastatin or gemfibrozil) guar gum has shown some promise: it may produce a further reduction in total cholesterol of about 10% in patients not responding adequately to these drugs alone. Gastrointestinal effects, notably flatulence, occur relatively frequently and may be considered unacceptable by some patients. Standardization of formulations and methods of administration of guar gum is required to clarify its pharmacological and clinical properties. Thus, on the basis of presently available evidence guar gum as monotherapy may be considered at most modestly effective in reducing serum cholesterol levels. Nonetheless, further investigation of guar gum is warranted, particularly its use as an adjunct to produce additional reductions in serum cholesterol in patients not responding optimally to other lipid-lowering agents.

Animals↗
PubMed1990

Isradipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cardiovascular disease.

Isradipine, a dihydropyridine derivative, inhibits the inward calcium flux through 'slow' channels of cardiac and vascular tissue, thereby eliciting potent coronary, cerebral and peripheral vasodilatation. In comparison with other calcium channel blockers the drug offers the advantages of minimal cardiodepressant activity, a selective action on the coronary and skeletal muscle vasculature, and a prolonged vasodilatory action. Clinical trials indicate that isradipine is an effective antihypertensive agent, suitable as monotherapy or in combination with beta-blockers, diuretics or ACE inhibitors, for long term treatment of mild to moderate hypertension. Preliminary findings suggest that the drug has a potential role in the treatment of chronic stable angina and, possibly, congestive heart failure. Adverse effects associated with the vasodilatory action of isradipine are generally mild, transient and well-tolerated, and are similar to those encountered with other calcium channel blockers. Thus, isradipine appears to offer a useful alternative to other dihydropyridine derivatives currently employed for the treatment of mild to moderate hypertension and, to a lesser extent, chronic stable angina. While its relative freedom from serious adverse effects may prove of value, its place in therapy vis-à-vis the established calcium channel blockers requires further clarification.

Animals↗
PubMed1990

Zolpidem. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential.

Zolpidem is an imidazopyridine, a chemically novel nonbenzodiazepine hypnotic agent which acts at the benzodiazepine omega 1-receptor subtype in the brain. With a rapid onset of action and short elimination half-life, it reduces the latency to and prolongs the duration of sleep in patients with insomnia, yet has no major effects on sleep stages when given in dosages of 5 to 20 mg nightly. Rebound effects on withdrawal of the drug have not been observed. Unlike benzodiazepines, zolpidem has no myorelaxant or anticonvulsant effects and its effects on anxiety appear to be minor. While zolpidem aids sedation, and may reduce memory or psychomotor function within the first 2 hours after administration of single oral doses, its use as a surgical premedicant remains to be established. Adverse effects are predominantly CNS and gastrointestinal in nature. Altered pharmacokinetics may lead to an increase in dose-proportionate adverse effects in the elderly and in patients with renal dysfunction. Limited evidence to date suggests that the dependence liability of zolpidem is minimal. Thus, zolpidem is an interesting alternative to benzodiazepines in the treatment of insomnia, with properties that potentially offer worthwhile advantages in this therapeutic area if they are confirmed with wider clinical experience.

Drug Interactions↗
PubMed1989

Carboplatin. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of cancer.

Carboplatin is a 'second-generation' platinum compound advocated for use in the treatment of patients with ovarian cancer and it has also shown promise in small cell lung cancer, squamous cell carcinomas of the head and neck, and seminomas. Overall, it would appear to have a similar qualitative spectrum of activity to cisplatin. There have been few comparative trials with carboplatin, either alone or in combination with other chemotherapeutic agents, but the limited data suggest comparable efficacy with cisplatin in ovarian cancer. Importantly, the toxicity profile of carboplatin is markedly different from that of cisplatin, with nephrotoxicity, neurotoxicity and ototoxicity occurring only infrequently with carboplatin. As with cisplatin, nausea and vomiting occur in many patients after carboplatin administration, but symptoms are usually delayed for several hours and are mild to moderate in severity - dose-limiting nausea and vomiting are infrequent with carboplatin. The dose-limiting toxicity of carboplatin is myelosuppression, with severe thrombocytopenia and less often leucopenia, which may be more severe in older patients or in those with renal impairment or those who have had previous chemotherapy. Thus, preliminary data suggest that carboplatin is a therapeutically equivalent alternative to cisplatin, but with a differing toxicity profile that should offer advantages over cisplatin in many patients.

Carboplatin↗
PubMed1989

Labetalol. A reappraisal of its pharmacology, pharmacokinetics and therapeutic use in hypertension and ischaemic heart disease.

Since labetalol was first reviewed in the Journal (1978), its scope of therapeutic use has expanded and become better defined. Labetalol is an adrenoceptor blocking drug with combined alpha- and beta-blocking properties. These result in a more favourable haemodynamic profile for labetalol compared with 'pure' beta-blockers or pure alpha-blockers, but also contribute to a wider range, but not an overall increased incidence, of adverse effects. The drug is effective and well-tolerated in patients with all grades of hypertension, but is of particular value in special subgroups such as Black patients, the elderly and patients with renal hypertension. While comparative studies are not extensive, available data show that the drug reduces blood pressure to a similar extent, and in a similar proportion of patients, as 'pure' beta-blockers such as propranolol, pure alpha-blockers such as prazosin, calcium antagonists (nifedipine, verapamil), and centrally acting drugs (clonidine and methyldopa). Labetalol is very effective in hypertensive pregnant women and in hypertensive crises, where it provides good control of blood pressure without serious adverse effects, and where few therapeutic options exist. Few controlled studies have investigated the use of labetalol in deliberate induction of hypotension or prevention of hypertension during anaesthesia, and also in patients with ischaemic heart disease. However, available evidence suggests a role for labetalol in these indications and further studies should aid in clarification of its efficacy in these areas. Thus, with its broad scope of therapeutic use in hypertension labetalol remains an important therapeutic option, and the drug may well find an additional place in the treatment of myocardial ischaemia if further evidence confirms encouraging preliminary findings.

Coronary Disease↗
PubMed1989

Dezocine. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy.

Dezocine is an analgesic agent with opioid agonist and antagonist activity. After parenteral administration of therapeutic doses it is approximately equipotent with morphine, and has proved at least as effective an analgesic as morphine, pethidine (meperidine) and butorphanol in moderate to severe postoperative pain. However, preliminary pharmacodynamic data indicate that the ceiling of analgesic activity of dezocine occurs at a higher level of analgesia than that of reference agonist/antagonist agents. Also, the drug exhibited a morphine-like degree of anaesthetic-sparing activity in animals. Although long term data are very limited, single doses of dezocine are well tolerated, with mild and transient sedation and gastrointestinal upset the principal adverse effects. As with some other agonist/antagonist analgesics, a 'ceiling' effect to dezocine-induced respiratory depression occurs with increasing dosage, beyond which further depression has not been observed. In single analgesic doses, however, dezocine is a slightly more potent respiratory depressant than morphine. Clinically important haemodynamic changes have not been observed with usual analgesic doses of dezocine. As an agonist/antagonist opioid, the dependence liability of dezocine would be expected to be lower than that of pure agonist opioids, but extended clinical use is required before more definitive conclusions can be drawn in this regard. Unlike older drugs of its type, dezocine produced opiate-like subjective effects and was identified as morphine-like by drug abusers. Thus, provided the promising conclusions of currently available clinical studies are confirmed with its wider use, dezocine should be a useful additional agent for the treatment of moderate to severe postoperative pain.

Analgesics↗
PubMed1989

S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism.

S-Adenosyl-L-methionine (SAMe) is a naturally occurring molecule distributed to virtually all body tissues and fluids. It is of fundamental importance in a number of biochemical reactions involving enzymatic transmethylation, contributing to the synthesis, activation and/or metabolism of such compounds as hormones, neurotransmitters, nucleic acids, proteins, phospholipids and certain drugs. The administration of a stable salt of SAMe, either orally or parenterally, has been shown to restore normal hepatic function in the presence of various chronic liver diseases (including alcoholic and non-alcoholic cirrhosis, oestrogen-induced and other forms of cholestasis), to prevent or reverse hepatotoxicity due to several drugs and chemicals such as alcohol, paracetamol (acetaminophen), steroids and lead, and to have antidepressant properties. In all of these studies SAMe has been very well tolerated, a finding of great potential benefit given the well-known adverse effects of tricyclic antidepressants with which it has been compared in a few trials. Thus, with its novel mechanisms of action and good tolerability, SAMe is an interesting new therapeutic agent in several diverse disease conditions, but its relative value remains to be determined in appropriate comparisons with other treatment modalities in current use.

Animals↗