Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sertraline hydrochloride is a new naphthylamino compound that specifically blocks neuronal reuptake of serotonin. It is currently available in the United Kingdom and under review in the US. Sertraline follows first-order kinetics, with a plasma elimination half-life of 24-26 hours. It is highly bound to plasma proteins and has a large volume of distribution. Multicenter studies conducted by the manufacturer have shown sertraline to be efficacious in the treatment of depression and obsessive-compulsive disorder. The daily dose will range from 50 to 200 mg/d for the treatment of depression. The adverse-effect profile differs greatly from the tricyclic antidepressants, but is similar to that of fluoxetine. The most prominent adverse effects are gastrointestinal (nausea, diarrhea/loose stools, dyspepsia).
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PMID:Sertraline: a new specific serotonin reuptake blocker. 194 75

The antidepressants clomipramine hydrochloride (Anafranil), fluoxetine hydrochloride (Prozac), and sertraline hydrochloride (Zoloft) are the main choices for pharmacologic treatment of obsessive-compulsive disorder. Often, drug doses for obsessive-compulsive disorder are higher than for depression, and improvement occurs more slowly and is often only partial. Behavior therapy involving exposure to feared objects or situations and prevention of ritualistic behavior complements pharmacologic treatment. Referral to a behavioral therapist may be necessary to achieve recovery.
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PMID:Obsessive-compulsive disorder. How to free patients from intrusive thoughts and rituals. 799 73

Hemodialysis hypotension (HH) is a very common disorder and has a multifactorial etiology. Autonomic dysfunction occurs in up to 50% of patients with end-stage renal disease (ESRD) and plays a key role in HH in some patients. Sertraline hydrochloride, a central nervous system serotonin reuptake inhibitor, has been shown to be an effective treatment of hypotension caused by autonomic dysfunction in disorders such as neurocardiogenic syncope and idiopathic orthostatic hypotension. This study sought to determine whether sertraline was effective in ameliorating HH. A retrospective chart analysis was performed that included nine consecutive patients (aged > or = 54 years, time on hemodialysis > or = 2.2 years) placed on sertraline (50 to 100 mg/d) for depression who also had HH (defined as prehemodialysis systolic blood pressure [SBP] < or = 100 mm Hg, > or = 40 mm Hg decrease in SBP during hemodialysis, SBP <90 mm Hg, any diastolic blood pressure <40 mm Hg, or a decrease in blood pressure-causing symptoms) before treatment with sertraline. The data from a 6-week pre-sertraline period were compared with the data from a 6-week sertraline period (defined as 6 weeks after drug begun). Blood pressure medications were unchanged during the trial period of sertraline. However, nadir mean arterial pressure recorded during a given dialysis session in the pre-sertraline period (55+/-4 mm Hg) was significantly lower than that recorded in the sertraline period (68+/-5 mm Hg; P < 0.05). In addition, the number of hypotensive episodes (same definition as HH) per dialysis session during the sertraline period was significantly lower than that during the pre-sertraline period (mean, 0.6+/-0.2 episodes per session v 1.4+/-0.3 episodes per session; P < 0.005). The number of therapeutic interventions required for hypotension during the sertraline period was also significantly less than that during the pre-sertraline period (mean, 1.7+/-0.8 interventions v 11.0+/-3.0 interventions; P < 0.005). The urea reduction ratio (62.7%+/-4.7% v 63.1%+/-9.3%; P = NS) and hematocrit (28.9%+/-0.8% v 29.5%+/-1.0%; P = NS) did not change significantly. It is concluded that the short-term (6 weeks) use of sertraline hydrochloride reduces HH in some patients with ESRD. A possible mechanism for this effect is sertraline-induced attenuation of the paradoxical sympathetic withdrawal that may underlie HH in some patients with ESRD.
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PMID:Effect of sertraline hydrochloride on dialysis hypotension. 953 Nov 78

Obsessive compulsive disorder (OCD) is characterized by recurrent and intrusive thoughts that are distressing (obsessions) and/or repetitive behaviors or mental acts that the person feels driven to perform (compulsions). OCD has a partly genetic basis. For treatment of OCD, potent serotonin reuptake inhibitor (SRI) drugs (clomipramine (Anafranil), fluvoxamine (Luvox), fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil)), which act on the serotonin transporter protein, are uniquely efficacious. A polymorphism in the promoter region of the gene (SLC6A4) encoding this protein, was recently reported to affect protein expression and to be associated with measures of anxiety and depression and with autism (using a family-controlled transmission disequilibrium test (TDT) design). SLC6A4 therefore has strong a priori support for potentially influencing risk for OCD: the protein it encodes is a medication target; a polymorphism in the gene affects function; and that polymorphism has been shown to be associated with behavioral phenotypes. We used the TDT with a set of 34 European-American family trios, 30 unrelated and four drawn from an extended pedigree, to test for linkage disequilibrium between OCD and alleles at the SLC6A4 promoter polymorphic locus. Of 35 heterozygous parents, 24 transmitted the 'l' SLC6A4 allele and 11 transmitted the 's' allele (chi 2 TDT = 4.83; P < 0.03). Considering only the 13 SRI drug nonresponders, there were 13 heterozygous parents, of whom 10 transmitted the 'l' allele and three the 's' allele (chi 2 TDT = 3.77; P < 0.052). These data provide preliminary support for association and linkage disequilibrium between the SLC6A4 'l' allele and OCD.
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PMID:Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder. 967 4

Sertraline (Zoloft, Pfizer) has been shown in numerous controlled studies to have similar efficacy to other selective serotonin (5-HT) re-uptake inhibitors (SSRIs) in the treatment of depression and anxiety disorders. Further research is indicating that the efficacy of sertraline extends even beyond the treatment of depression and anxiety to include utility in eating disorders, premenstrual dysphoric disorder (PMDD) and possibly substance abuse treatment. Along with other SSRIs, sertraline offers several advantages over older antidepressants, including improved patient tolerability, low risk of lethality in overdose and no dependence potential. In head-to-head comparisons, sertraline appears to be at least as well-tolerated as other SSRIs and may even have a more favourable side effect profile. Low potential for pharmacokinetic drug interactions is another advantage of sertraline. Unlike fluoxetine, fluvoxamine and paroxetine, sertraline is not a potent inhibitor of any of the cytochrome P450 isoenzyme systems. As a result of its proven efficacy, good tolerability and lack of pharmacokinetic interactions, sertraline should be considered first-line in the treatment of anxiety and depressive disorders.
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PMID:Review of sertraline and its clinical applications in psychiatric disorders. 1133 29

Recent studies have suggested that serotonin reuptake inhibitors (SSRI's), prescribed for the relief of depression, can cause sexual dysfunction in up to fifty percent of those taking them. The SSRI's--including fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil)--affect mood stabilization by promoting the transmission of the neurotransmitter serotonin, although enhancing serotonergic function can decrease libido or lead to erectile difficulties. As an alternative to lowering antidepressant dosages and risking losing therapeutic gains, administering serotonin-blockers, such as cyproheptadine (Periactin) and yohimbine (Yocon), has been shown to restore sexual function. However, the serotonin antagonist, cyproheptadine, causes sedation and can reverse the antidepressant or anti-obsessive effect of the SSRI. Yohimbine enhances transmission of the neurotransmitter epinephrine, increasing the flow of blood to erectile tissue and stimulating sexual desire by activating the cerebral cortex. Its drawbacks are increased levels of panic attacks and higher required dosages. Other potential biochemical stratagems are: amantadine (Symmetrel), bromcriptine (Parlodel), and buspirone (Buspar), which enhance dopamine and serotonin transmission; and bethanecol (Urechline), which enhances choline transmission. One study indicates improved sexual response when the nonserotonergic, mildly dopamine-enhancing buproprion (Welbutrin) is substituted for fluoxetine.
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PMID:Depression, antidepressants, and sexual function. 1136 52

Two surveys of individuals with fibromyalgia were conducted to assess the frequency and prevalence of symptoms (N = 99) as well as healthcare providers, medications, and self-care activities used to manage one's fibromyalgia (N = 54). The pervasiveness of symptoms was striking, with 24 various symptoms ranging from cognitive to intestinal problems occurring in at least 75% of the respondents. Significant correlations were present between health status and both physical (P = .002) and psychological (P =.008) symptoms. There was also a significant correlation between the total number of symptoms and the degree of life disruption attributed to fibromyalgia (P =.015). A variety of healthcare professionals were seen, with internists, family physicians, and rheumatologist most frequently used. Although at least 80% of the respondents reported difficulty with anxiety, confusion, irritability, depression, and cognitive difficulties, less than 10% of the respondents reported seeing a psychiatrist. Most frequently used medications were: amitriptyline, (fluoxetine HCl) Prozac, ibuprofen (Motrin), sertraline HCI (Zoloft), and zolpidem (Ambein). Self-care activities used with the most success were walking, stretching, and exercising. These studies indicate the need for more research and support for healthcare providers as well as patients with fibromyalgia.
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PMID:Fibromyalgia: patient perspectives on symptoms, symptom management, and provider utilization. 1183 25

Zoloft (sertraline hydrochloride) is one of the antidepressant medications used to treat depression, obsessive-compulsive disorder, and social anxiety disorder. The practice of embalming a cadaver is common, yet it may create problems for forensic toxicologists if the case was not previously suspected to involve drug overdose. According to the Eschweiler-Clarke reaction, drugs containing a secondary amine group react with formaldehyde to give N-methyl derivatives. Sertraline has a secondary amine group; therefore, we predicted that it may react with formalin to give N-methyl derivatives. The stability of sertraline in formalin solution was studied at three different concentrations (5%, 10%, and 20%) and at three different pHs (3.0, 7.0, and 9.5) for a period of 30 days. Setraline and its degraded products were extracted by liquid-liquid extraction using chloroform, and the concentrated extracts were analyzed by gas chromatography-mass spectrometry using electron impact ionization mode. The rate of conversion is rapid at higher pH. Sertraline was totally converted to the N-methyl derivative after 30 days in 10% and 20% formalin solutions at neutral and basic conditions. Therefore, forensic toxicologists should be cautious when performing a death investigation if formalin solution is the only sample available for analysis. This work shows that analysis for parent drug or its N-methyl derivative may provide data that will reduce the likelihood of false negatives.
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PMID:Conversion of sertraline to N-methyl sertraline in embalming fluid: a forensic implication. 1687 72

Sertraline is selective serotonin reuptake inhibitor drug marketed as Zoloft by Pfizer and used mainly for the treatment of depression, anxiety and obsession. A number of side effects are associated with the use of the drug including gastrointestinal complaints, nervousness and sexual dysfunction. This means that a reliable fast method (such as biosensing) for determining sertraline metabolic profile of patients is essential for adequate dosing. Nanobiosensor for the determination of sertraline biotransformation was prepared with cytochrome P450-2D6 (CYP2D6) and poly(8-anilino-1-napthalene sulphonic acid) nanotubes (90 nm in diameter and 600-800 nm in length) potentiodynamically deposited on gold. The biosensor gave a linear response over the concentration range of 0.2 and 1.4 microM with a sensitivity value of 0.301 microA/microM and a detection limit of 0.13 microM. The nanobiosensor exhibited substrate inhibition response profile for sertraline biotransformation at high concentrations. Analysis of the Michaelis-Menten region of the nanosensor response curve for sertraline gave an apparent Michaelis-Menten constant (K(m)) value of 0.75 microM, which is higher than the peak plasma concentration (C(max)) value of 0.55 microM, thereby making the sensor suitable for sertraline determination in serum.
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PMID:Amperometric responses of CYP2D6 drug metabolism nanobiosensor for sertraline: a selective serotonin reuptake inhibitor. 1767 7

Although a large literature supports the benefits of breastfeeding, this review suggests that breastfeeding is less common among postpartum depressed women, even though their infants benefit from the breastfeeding. Depressed mothers, in part, do not breastfeed because of their concern about potentially negative effects of antidepressants on their infants. Although sertraline (Zoloft) and paroxetine (Paxol) concentrations are not detectable in infants' sera, fluoxetine (Prozac) and citalopram (Celexa) do have detectable levels. Unfortunately these findings are not definitive because they are based on very small sample, uncontrolled studies. As in the literature on prenatal antidepressant effects, the question still remains whether the antidepressants or the untreated depression itself has more negative effects on the infant. It is possible that the positive effects of breastfeeding may outweigh the positive effects of the antidepressants for both the mother and the infant. In addition, some alternative therapies may substitute or attenuate the effects of antidepressants, such as vagal stimulation or massage therapy, both therapies being noted to reduce depression. Further studies of this kind are needed to determine the optimal course of therapy for the benefit of the depressed, breastfeeding mother and the breastfed infant.
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PMID:Breastfeeding and antidepressants. 1827 27


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