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
Ssri sexual dysfunction remedy herbicide 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.
Since their introduction, it has become apparent that these drugs have certain advantages over the older tricyclic antidepressants and monoamine oxidase inhibitors, notably in the area of safety and tolerability.
Most clinicians now consider the SSRIs and some of the other new antidepressants first-line treatment for depression and anxiety disorders. However, the issue of safety and tolerability, and indeed efficacy, becomes more
Ssri sexual dysfunction remedy herbicide when comparing members of the newer generations of antidepressants.
Not only are SSRIs chemically different from the tricyclic, tetracyclic and other antidepressant agents, considerable structural differences also exist between the various SSRIs. For example, fluvoxamine is the only monocyclic SSRI and belongs to the 2-aminoethyl oxime ethers of aralkylketones. Therefore, some differential pharmacology between the drugs in the same class may be expected.
The aim of this review, which was based on a Medline literature search, is to provide a comprehensive comparative overview of the main clinical features of some antidepressants based on pharmacology, pharmacokinetics, tolerability and safety. Most of the effects of antidepressants, whether therapeutic or adverse, can be directly related to their pharmacology.
Although the ultimate mechanism of action of antidepressants remains uncertain, it is reasonable to assume that the effects on monoamine systems in the brain are central to their therapeutic effects. Venlafaxine, for instance, is one of the most potent antidepressants at blocking the dopamine transporter, and paroxetine, although the most potent blocker of 5-HTT, also has appreciable affinity for the noradrenaline transporter NAT 1.
In comparison with the other SSRIs, paroxetine has the highest affinity for the muscarinic receptor Figure 1 1which at higher dosages, or at low dosages in slow metabolisers, may lead to anticholinergic side effects such as dry mouth, constipation, dizziness, tachycardia, blurred vision, urinary retention and
Ssri sexual dysfunction remedy herbicide 7.
Anticholinergic side effects also include memory impairment 78confusion 7problems with concentration 7 and sexual dysfunction, but these side effects are less likely to occur at normal dosages of paroxetine 9 — Compared with other antidepressants, paroxetine also has an affinity for binding at the NAT Figure 2 1.
Relative potency of the antidepressants for binding at muscarinic receptors. Potency of antidepressants for binding at muscarinic receptors based on IC 50 values: Relative potency of the antidepressants for binding at the noradrenaline transporter.
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Potency of antidepressants at noradrenaline transporter based on IC 50 values: This property, which may cause somnolence 13sedation 1314sexual dysfunction 10weight gain 1516memory impairment 17attention deficit 17 and psychomotor alterations 1819has no or only minor clinical significance for citalopram at normal dosages.
Relative potency of the antidepressants for binding histaminergic H1 receptors. Potency of antidepressants for binding H1 receptors based on
Ssri sexual dysfunction remedy herbicide i values: Paroxetine has the lowest affinity for this binding site Although the clinical significance of binding to this receptor remains uncertain, it might account for the superior efficacy of fluvoxamine in psychotic depression 21 The half-lives of fluvoxamine, paroxetine, sertraline and citalopram are all approximately 1 day.
The half-life of fluoxetine is approximately 2 days after a single dose and 6 days after multiple dosing The half-life of venlafaxine is relatively short about 4 hand hence this drug requires twice daily b.
Fluoxetine has a pharmacological active metabolite, norfluoxetine, which has a half-life of 7—15 days 23 — Sertraline also has an active metabolite 26citalopram has three active metabolites 27and escitalopram has two Of the seven metabolites identified from venlafaxine, at least three
Ssri sexual dysfunction remedy herbicide them are pharmacologically active A long half-life of the parent compound or the presence of active metabolites may cause accumulation, which is associated with an increased risk of late-emergent side effects, may be cardiotoxic especially in case of overdose and may have clinically unexpected consequences
Ssri sexual dysfunction remedy herbicide significant longer half-lives of fluoxetine and its metabolite, norfluoxetine, are associated with a significantly slower onset of action in comparison with other SSRIs A double-blind study comparing SSRIs in patients with depression have shown that fluoxetine has a significantly slower onset of therapeutic action compared with fluvoxamine
Ssri sexual dysfunction remedy herbicide In fact, a slower onset of action with fluoxetine compared with the other SSRIs has been reported in a recent Ssri sexual dysfunction remedy herbicide of 20 comparative studies Moreover, the gradual accumulation of norfluoxetine may produce a high ratio of norfluoxetine: With the possible exception of citalopram, SSRIs are relatively safe in cases of overdose 35 — Citalopram's active metabolite, didesmethylcitalopram, has played an "Ssri sexual dysfunction remedy herbicide" role in several cases of cardiotoxicity 29because it may cause a QT prolongation 3537 After discontinuation, residual amounts of fluoxetine and norfluoxetine in the plasma may increase the potential toxicity of subsequent TCA overdose due to pharmacokinetic drug—drug interactions It is worth noting that the metabolites of sertraline desmethylsertraline Ssri sexual dysfunction remedy herbicide, fluoxetine norfluoxetine and paroxetine all inhibit cytochrome P CYP isoenzymes, notably CYP 2D6 Although this issue is considered of minimal clinical significance, there are reports of important adverse events related to protein-binding displacement interactions The interactions related to CYP liver enzymes may have no effect, lead to intoxication or improve the therapeutic response of a given agent.
The different pharmacokinetic profiles of the antidepressants, especially their potential for drug—drug interactions, should always be considered especially when multiple drugs are prescribed The CYP 2D6 subenzyme metabolises numerous drugs, including many typical and atypical antipsychotics e.
Interindividual variation in the gene that encodes CYP 2D6 plays an important role in the variable drug treatment responses In fact, CYP 2D6 polymorphisms may contribute to development
Ssri sexual dysfunction remedy herbicide adverse effects or may be a reason for the poor efficacy of antidepressant treatment Paroxetine and fluoxetine and norfluoxetine are very potent inhibitors of CYP 2D6 4247 — Of all SSRIs, fluvoxamine has the lowest potential for drug interactions involving this enzyme CYP 2D6 may play a minor in the metabolism of citalopram, but one of its main metabolites, N -desmethylcitalopram, is further extensively metabolised by CYP 2D6 to didesmethylcitalopram 45 Indeed, in a recent publication, pharmacokinetic interactions were found for citalopram due to CYP 2D6 The interactions with CYP 2D6 may be clinically significant not only for citalopram but also for escitalopram CYP 2D6 is the major enzyme involved in the metabolism of venlafaxine Although venlafaxine is considered by some investigators to be a weak inhibitor of CYP 2D6 43CYP 2D6 plays an important role in the formation of O -desmethylvenlafaxine that is one of venlafaxine's major metabolites Decreased CYP 2D6 activity has been associated with cardiovascular toxicity observed during treatment with venlafaxine As the effect of the SSRIs on hepatic CYP enzymes differ markedly and may be clinically important, selection of the antidepressant should be appropriate for the patient The most common adverse event reported during treatment with SSRIs is nausea, which tends to disappear after some days of treatment The overall incidence of nausea is similar for all SSRIs 61occurring quite frequently as a consequence of increased availability of 5-HT in the gastrointestinal tract and also probably in central nervous system.
Stimulation of 5-HT 3 receptors plays a pivotal role in the development of this side effect, as antagonists for this receptor are capable of reducing the effect Nausea is also among the most common adverse reactions for venlafaxine 63 Depressed male patients are almost twice as likely to present with erectile dysfunction compared with non-depressed men Furthermore, patients treated with an SSRI may present with sexual dysfunction as an unwanted side effect of therapy.
Paroxetine, sertraline and citalopram are reported to cause delayed ejaculation. The SSRIs are reported to cause sexual dysfunction in the following descending order of frequency: The SNRI, venlafaxine, has been associated with impotence, abnormal ejaculation and orgasm, especially at higher doses, and it is reported to have an incidence of sexual side effects at least as high as that seen with paroxetine and sertraline Sexual side effects should be taken into consideration before prescribing a drug treatment for depression, because sexual dysfunction may play an important role in compliance with treatment and can act as an additional stress factor for the patient In contrast to the tricyclic antidepressants, SSRIs at normal clinical doses have little effect on cognitive psychomotor functioning.
However, sertraline, "Ssri sexual dysfunction remedy herbicide" and fluoxetine have all shown some alerting effects and excitation 7374 that may be detrimental in elderly patients. Indeed, fluoxetine has been reported to be associated with an increased incidence of nervousness and insomnia compared with the tricyclic antidepressants 75 Paroxetine has also been shown to impair cognition and vigilance, which may also be particularly problematic in elderly patients
Ssri sexual dysfunction remedy herbicide Drug-induced behaviour arousal features in activation, over motivation, pathological
Ssri sexual dysfunction remedy herbicide, compromised sexual function and cognitive impairment In contrast to sertraline, paroxetine and fluoxetine, fluvoxamine has been shown to have little or no effect on behavioural arousal Indeed, fluvoxamine has no effect on psychomotor speed, cognitive processing or arousal Similarly, fluvoxamine showed no potentiation of alcohol-related cognitive impairment As fluvoxamine 50 mg and mg was found not to impair psychomotor performance or cognitive ability in any relevant tests, including choice reaction time, tracking, critical flicker fusion threshold and memory scanning, it may be of value for use in outpatients who wish to carry out the tasks of everyday life.
In a double-blind study comparing dothiepin and venlafaxine in elderly patients, venlafaxine Evidence suggests that fluvoxamine has beneficial effects on sleep in depressed patients. A recent double-blind study comparing fluvoxamine and fluoxetine showed that depressed patients treated with fluvoxamine improved their sleep quality both significantly more and more rapidly than patients on fluoxetine Another direct comparative study involving fluvoxamine and paroxetine 72 showed that paroxetine caused a greater disruption of sleep patterns than fluvoxamine, and the paroxetine-induced sleep disruption persisted into the withdrawal phase The beneficial effects of fluvoxamine on sleep quality have also been reported in patients with post-traumatic stress disorder PTSD.
Fluvoxamine was effective in reducing all three symptom clusters of PTSD intrusion, avoidance and hyperardusalincluding nightmares and insomnia In addition, patients suffering from other anxiety disorders, such as obsessive-compulsive disorder and panic disorder, have been found to experience a significant reduction of insomnia when treated with fluvoxamine It has been suggested that the beneficial effects of fluvoxamine on sleep may be related to its inhibitory effect on melatonin degradation; this effect has not been observed with other SSRIs 85 In a double-blind placebo-controlled study, venlafaxine was found to decrease sleep continuity, markedly increase the time to rapid eye movement REM sleep and decrease the duration of total REM sleep Other more recent publications confirm that venlafaxine worsens sleep quality 88 — Changes in bodyweight are associated with a low acceptance of treatment and an increased risk of non-compliance during long-term treatment by patients Typically, SSRIs mediate a reduction in food intake, particularly in the initial phase of therapy.
However, weight is frequently regained after 6 months of treatment and can be followed by additional weight gain during long-term treatment Paroxetine, fluoxetine, citalopram and sertraline have been shown to significantly increase bodyweight after 6—12 months of administration Weight gain could be related to carbohydrate craving, as reported for citalopram However, an alteration in metabolic rate may be responsible for the weight changes In this regard, fluvoxamine
Ssri sexual dysfunction remedy herbicide reported to promote an increase in resting
Ssri sexual dysfunction remedy herbicide rate, resulting in less weight gain Of the SSRIs, paroxetine may be responsible for the highest amounts of weight gain 92 However, follow-up over 2 years of patients receiving open-label clomipramine, citalopram, fluoxetine, fluvoxamine, paroxetine or sertraline showed that clomipramine was associated with the highest weight increase and fluoxetine and sertraline with the lowest Key words: Erectile dysfunction, integrative medicine, medicinal plants, minerals, magnesium, natural therapy.
use of G. biloba for antidepressant, especially SSRI (serotonin . herbicides, petroleum-based products), ED induced by. Common adverse effects of SSRIs include gastrointestinal upset, sexual dysfunction, bleeding, emotional blunting, cognitive dysfunction, and changes in energy.
Antidepressant therapy is not a panacea for treating patients with depression.
an SSRI, which, like other drugs in its class, can induce a plethora of sexual Although dry mouth, drowsiness, and sexual dysfunction were most common, it was . Do ultra-short screening instruments accurately detect depression in primary.
ANTIDEPRESSANT THERAPY IS NOT A PANACEA FOR TREATING PATIENTS WITH DEPRESSION. . AN SSRI, WHICH, LIKE OTHER... FLUVOXAMINE MAY HAVE FEWER EFFECTS ON SEXUAL DYSFUNCTION AND SLEEP PATTERN. . CONVERSELY, ABOUT 5% ARE... EDITORIAL NOTE: I SAW MY FIRST CASE OF POST-SSRI SEXUAL DYSFUNCTION (PSSD) 15 WHEN WE TRIED... KEY WORDS: ERECTILE DYSFUNCTION, INTEGRATIVE MEDICINE, MEDICINAL PLANTS, MINERALS, MAGNESIUM, NATURAL THERAPY, .. USE OF G. BILOBA FOR...
Particular serotonin [5-hydroxytryptamine 5-HT ] reuptake inhibitors SSRIs and the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in treatment for gloom. The highly specific enterprises of SSRIs of enhancing serotonergic neurotransmission appears to explain their benefit, while lack of direct enterprises on other neurotransmitter systems is responsible for their superior safety profile compared with tricyclic antidepressants.
Although SSRIs and venlafaxine sire similar adverse effects, undoubting differences are emerging. Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern.
SSRIs pull someone's leg a cardiovascular safety improve take advantage of 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 grow up upon abrupt SSRI cessation. SSRIs are more adequate 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 portrayal and toxicity.
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Changes in bodyweight are associated with a low acceptance of treatment and an increased risk of non-compliance during long-term treatment by patients In contrast, in a retrospective review of patients, citalopram was associated with a significantly longer QT interval on ECG recording, but mean QTc durations were not significantly different between all drugs studied.
In fact, a slower onset of action with fluoxetine compared with the other SSRIs has been reported in a recent meta-analysis of 20 comparative studies Interindividual variation in the gene that encodes CYP 2D6 plays an important role in the variable drug treatment responses Venlafaxine treatment of binge-eating disorder associated with obesity:
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pram treatment, Mr. B has had no sexual side effects, and his mood and anxiety other SSRIs to cause sexual dysfunction (S. Pallanti et al., un- published report, ). .. copy, colonoscopy, abdominal CT scan, pelvic ultra- sound, and a. Tolerability and safety of fluvoxamine and other antidepressants strings, encompassing the terms “female sexual dysfunction” and “treatment,” in combination with “vulvovaginal .. ultra-low dose . sexual quality of life for females; SSE = satisfying sexual events; SSRI = selective serotonin reuptake inhibitor;. treatments for hypoactive sexual desire disorder and female sexual arousal disorder in women with SSRI-induced sexual dysfunction. A preliminary study Free testosterone was determined in plasma through ultra-filtration followed by. Common adverse effects of SSRIs include gastrointestinal upset, sexual dysfunction, bleeding, emotional blunting, cognitive dysfunction, and changes in energy. Context: Erectile dysfunction (ED) and premature ejaculation (PE) are the two most prevalent male sexual dysfunctions. . information about vascular status; however, duplex ultra- .. Daily SSRIs are the first choice of treatment in PE but are.
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