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

We present the case of a 35-year-old woman who developed serotonin syndrome after receiving a single dose of the cyclic antidepressant imipramine (Tofranil). She was already being treated for depression with paroxetine (Paxil), a selective serotonin reuptake inhibitor. Two hours after receiving imipramine, the patient developed tachycardia, delirium, bizarre movements, and myoclonus, all classic findings of serotonin syndrome. Her antidepressants were discontinued and she was treated with intravenous fluids, sedation, and a short course of cyproheptadine, a serotonin receptor antagonist. All symptoms resolved completely within 24 hours. In this case report, we review the drug interactions that can precipitate serotonin syndrome, and give recommendations for the diagnosis and treatment of this potentially fatal disorder.
 ...
PMID:Serotonin syndrome: case report and review of the literature. 941 60

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.
 ...
PMID:Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder. 967 4

Paroxetine (Paxil) is a selective serotonin reuptake inhibitor, one of a new class of antidepressants used in the treatment of obsessive-compulsive disorder, panic disorder, and depression. Paroxetine potentiates serotonergic activity through the selective inhibition of serotonin reuptake in the central nervous system. There are few reported overdoses in the literature, and of these, three were fatal. Three coroner's cases in which paroxetine was directly associated with the cause of death are reported. In case #1, paroxetine was the only drug detected in significant concentrations. The heart blood paroxetine concentration was 4.0 mg/L. Case #2 was a known suicide in which the decedent herself admitted taking pills and alcohol. The hospital blood sample drawn at admission was analyzed and contained a 0.25% ethanol level and no paroxetine. Death occurred 10 h later. The postmortem heart blood contained ethanol at 0.06%, paroxetine at 3.7 mg/L, fluoxetine at 0.86 mg/L, and norfluoxetine at 0.65 mg/L. In case #3, death was attributed to an apparent adverse drug interaction between paroxetine and imipramine/desipramine. The postmortem heart blood contained paroxetine at 1.4 mg/L, imipramine at 3.0 mg/L, and desipramine at 9.6 mg/L.
 ...
PMID:Distribution of paroxetine in three postmortem cases. 1044 95

Depressed mood has been associated with reduced natural killer cell activity (NKCA). Further, amelioration of depressive symptoms by pharmacotherapy has resulted in augmented NKCA. Serotonin, an indoleamine implicated in the pathophysiology of affective disorders, enhances NKCA in vitro and lymphocytes possess serotonin transporters and receptors. The present study evaluated NKCA in depressed outpatients before and during treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac(R)). Further, the SSRIs, fluoxetine and paroxetine (Paxil(R)), were also incubated in vitro with lymphoid cells to evaluate possible direct effects of SSRIs on NKCA. Depressed outpatients were administered fluoxetine (20 mg/day) for 4 weeks. NKCA and severity of depression were evaluated at weeks 0, 1, 2, and 4. Serum concentrations of fluoxetine and norfluoxetine were obtained as well. Mononuclear cells obtained from nonpatient volunteers were incubated with pharmacologic concentrations of fluoxetine or paroxetine and NKCA measured with a standard chromium release assay. Fluoxetine treatment resulted in decreased symptoms of depression and increased serum concentrations of fluoxetine and norfluoxetine. Further, fluoxetine treatment was associated with augmented NKCA in a subgroup of depressed outpatients exhibiting low NKCA at baseline. Fluoxetine had no effect on NKCA in depressed individuals exhibiting high NKCA at baseline. Incubation of mononuclear cells with fluoxetine and paroxetine augmented NKCA in vitro. The enhancing effects of antidepressants on NKCA in vivo and in vitro indicate a possible direct drug interaction with lymphoid cells during pharmacotherapy, suggesting that pharmacologic treatment of depression may result in enhanced immune competence as indexed by enhanced NKCA and that NKCA could be pharmacologically augmented with antidepressants in individuals with compromised immune function.
 ...
PMID:Antidepressants augment natural killer cell activity: in vivo and in vitro. 989 55

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.
 ...
PMID:Depression, antidepressants, and sexual function. 1136 52

The authors assessed the impact of osteopathic manipulative treatment (OMT) as an adjunct to standard psychiatric treatment of women with depression. Premenopausal women with newly diagnosed depression were randomly assigned to either control (osteopathic structural examination only; n = 9) or treatment group (OMT; n = 8). Both groups received conventional therapy consisting of the antidepressant paroxetine (Paxil) hydrochloride plus weekly psychotherapy for 8 weeks. Attending psychiatrists and psychologists were blinded to group assignments. No significant differences existed between groups for age or severity of disease. After 8 weeks, 100% of the OMT treatment group and 33% of the control group tested normal by psychometric evaluation. No significant differences or trends were observed between groups in levels of cytokine production (IL-1, IL-10, IL-2, IL-4, and IL-6) or in levels of anti-HSV-1, anti-HSV-2, and anti-EBV antibody. There was no pattern to the osteopathic manipulative structural dysfunctions recorded. The findings of this pilot study indicate that OMT may be a useful adjunctive treatment for alleviating depression in women.
 ...
PMID:Adjunctive osteopathic manipulative treatment in women with depression: a pilot study. 1157 38

Paroxetine hydrochloride hemihydrate (the active ingredient in Paxil) is a pharmaceutical compound used for the treatment of depression, social anxiety disorder, obsessive compulsive disorder, panic disorder, and generalized anxiety disorder. Paroxetine (PA) is extensively metabolized in humans, with about 97% of the parent compound being excreted as metabolites through the urine and feces of patients. Therefore PA and metabolites have the potential to be discharged into wastewater treatment systems after therapeutic use. PA and its major human metabolite (PM) were investigated using studies designed to describe physical/chemical characteristics and determine their fate and effects in the aquatic environment. A significant portion of the PM entering a wastewater treatment plant would be expected to biodegrade given the higher activated sludge solids concentrations present in a typical wastewater treatment plant. The potential for direct photolysis of PM is also possible based on photolysis results for PA itself. These results provide strong support for expecting that PA and PM residuals will not persist in the aquatic environment after discharge from a wastewater treatment facility. This conclusion is also supported by the results of a USGS monitoring study, where no PM was detected in any of the samples at the 260 ng/L reporting limit. The results presented here also demonstrate the importance of understanding the human metabolism of a pharmaceutical so that the appropriate molecule(s) is used for fate and effects studies. In addition to the PA fate studies, PM was investigated using studies designed to determine potential environmental effects and a predicted no effect level (PNEC). The average measured activated sludge respiration inhibition value (EC50) for PM was 82 mg/L. The measured Microtox EC50 value was 33.0 mg/L, while the Daphnia magna EC50 value was 35.0 mg/L. The PNEC for PM was calculated to be 35.0 microg/L. Fate data were then used in a new watershed-based environmental risk assessment model, PhATE, to predict environmental concentrations (PECs). Comparison of the calculated PECs with the PNEC allows an assessment of potential environmental risk. Within the 1-99% of stream segments in the PhATE model, PEC values ranged from 0.003 to 100 ng/L. The risk assessment PEC/PNEC ratios ranged from approximately 3 x 10(-8) to approximately 3 x 10(-3), indicating a wide margin of safety, since a PEC/PNEC ratio <1 is generally considered to represent a low risk to the environment. In addition, Microtox studies carried out on PM biodegradation byproducts indicated no detectable residual toxicity. Any compounds in the environment as a result of the biodegradation of PM should be innocuous polar byproducts that should not exert any toxic effects.
 ...
PMID:Environmental risk assessment of paroxetine. 1526 Mar 35

Recent studies suggest several problems associated with selective serotonin reuptake inhibitors (SSRIs) when administered during pregnancy. During organogenesis, paroxetine (Deroxat, Paxil, or generics) was associated with a significantly increased risk of major congenital malformations. Such an increase had already been reported with clomipramine (Anafranil), a tricyclic antidepressant. After the time of organogenesis, SSRIs have also been associated to risks. Of these, the more frequent is neonatal toxicity, while pulmonary hypertension in the newborn is likely to be the more severe. These newly discovered side effects arouse questions about the treatment of depression during pregnancy.
 ...
PMID:[Selective serotonin reuptake inhibitors (SSRIs) in pregnancy]. 1668 31

The mainstays of treatment for peripartum depression are psychotherapy and antidepressant medications. More research is needed to understand which treatments are safe, preferable, and effective. Postpartum depression, now termed peripartum depression by the DSM-V, is one of the most common complications in the postpartum period and has potentially significant negative consequences for mothers and their families. This article highlights common clinical challenges in the treatment of peripartum depression and reviews the evidence for currently available treatment options. Psychotherapy is the first-line treatment option for women with mild to moderate peripartum depression. Antidepressant medication in combination with therapy is recommended for women with moderate to severe depression. Although pooled case reports and small controlled studies have demonstrated undetectable infant serum levels and no short-term adverse events in infants of mothers breastfeeding while taking sertraline (Zoloft) and paroxetine (Paxil), further research is needed including larger samples and long-term follow-up of infants exposed to antidepressants via breastfeeding controlling for maternal depression. Pharmacologic treatment recommendations for women who are lactating must include discussion with the patient regarding the benefits of breastfeeding, risks of antidepressant use during lactation, and risks of untreated illness. There is a growing evidence base for nonpharmacologic interventions including repetitive transcranial magnetic stimulation, which may offer an attractive option for women who wish to continue to breastfeed and are concerned about their infants being exposed to medication. Among severe cases of peripartum depression with psychosis, referral to a psychiatrist or psychiatric advanced practice registered nurse is warranted. Suicidal or homicidal ideation with a desire, intent, or plan to harm oneself or anyone else, including the infant, is a psychiatric emergency, and an evaluation by a mental health professional should be conducted immediately. Peripartum depression treatment research is limited by small sample sizes and few controlled studies. Much work is still needed to better understand which treatments women prefer and are the most effective in ameliorating the symptoms and disease burden associated with peripartum depression.
...
PMID:Management of postpartum depression. 2413 8