Concept: Tricyclic antidepressant
Hypothesised associations between in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and congenital anomalies, particularly congenital heart defects (CHD), remain controversial. We investigated the putative teratogenicity of SSRI prescription in the 91 days either side of first day of last menstrual period (LMP).
Motor development in children prenatally exposed to selective serotonin reuptake inhibitors: a large population-based pregnancy cohort study
- BJOG : an international journal of obstetrics and gynaecology
- Published over 5 years ago
To estimate the association between prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and motor development in children considering the effect of maternal symptoms of anxiety and depression before, during and after pregnancy.
Antidepressant drugs such as selective serotonin re-uptake inhibitors (SSRIs) remediate negative biases in emotional processing in depressed patients in both behavioural and neural outcome measures. However, it is not clear if these effects occur before, or as a consequence of, changes in clinical state. Method In the present study, we investigated the effects of short-term SSRI treatment in depressed patients on the neural response to fearful faces prior to clinical improvement in mood. Altogether, 42 unmedicated depressed patients received SSRI treatment (10 mg escitalopram daily) or placebo in a randomised, parallel-group design. The neural response to fearful and happy faces was measured on day 7 of treatment using functional magnetic resonance imaging. A group of healthy controls was imaged in the same way.
To investigate the proposed synergistic teratogenic effect of use of selective serotonin receptor inhibitors (SSRI) together with sedatives or hypnotics, primarily benzodiazepines, during pregnancy.
Although selective serotonin reuptake inhibitors (SSRIs) are widely prescribed, associations with violence are uncertain.
To follow up on previously reported associations between periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and specific birth defects using an expanded dataset from the National Birth Defects Prevention Study.
- JAMA : the journal of the American Medical Association
- Published almost 7 years ago
IMPORTANCE Fibromyalgia is present in as much as 2% to 8% of the population, is characterized by widespread pain, and is often accompanied by fatigue, memory problems, and sleep disturbances. OBJECTIVE To review the epidemiology, pathophysiology, diagnosis, and treatment of fibromyalgia. EVIDENCE REVIEW The medical literature on fibromyalgia was reviewed from 1955 to March 2014 via MEDLINE and the Cochrane Central Registry of Controlled Trials, with an emphasis on meta-analyses and contemporary evidence-based treatment guidelines. Treatment recommendations are based on the most recent evidence-based guidelines from the Canadian Pain Society and graded from 1 to 5 based on the level of available evidence. FINDINGS Numerous treatments are available for managing fibromyalgia that are supported by high-quality evidence. These include nonpharmacological therapies (education, exercise, cognitive behavioral therapy) and pharmacological therapies (tricyclics, serotonin norepinephrine reuptake inhibitors, and gabapentinoids). CONCLUSIONS AND RELEVANCE Fibromyalgia and other “centralized” pain states are much better understood now than ever before. Fibromyalgia may be considered as a discrete diagnosis or as a constellation of symptoms characterized by central nervous system pain amplification with concomitant fatigue, memory problems, and sleep and mood disturbances. Effective treatment for fibromyalgia is now possible.
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used class of antidepressant drugs, but the cellular and molecular mechanisms by which their therapeutic action is initiated are poorly understood. Here we show that serotonin 5-HT1B receptors in cholecystokinin (CCK) inhibitory interneurons of the mammalian dentate gyrus (DG) initiate the therapeutic response to antidepressants. In these neurons, 5-HT1B receptors are expressed presynaptically, and their activation inhibits GABA release. Inhibition of GABA release from CCK neurons disinhibits parvalbumin (PV) interneurons and, as a consequence, reduces the neuronal activity of the granule cells. Finally, inhibition of CCK neurons mimics the antidepressant behavioral effects of SSRIs, suggesting that these cells may represent a novel cellular target for the development of fast-acting antidepressant drugs.
The role of serotonin in depression and antidepressant treatment remains unresolved despite decades of research. In this paper, we make three major claims. First, serotonin transmission is elevated in multiple depressive phenotypes, including melancholia, a subtype associated with sustained cognition. The primary challenge to this first claim is that the direct pharmacological effect of most symptom-reducing medications, such as the selective serotonin reuptake inhibitors (SSRIs), is to increase synaptic serotonin. The second claim, which is crucial to resolving this paradox, is that the serotonergic system evolved to regulate energy. By increasing extracellular serotonin, SSRIs disrupt energy homeostasis and often worsen symptoms during acute treatment. Our third claim is that symptom reduction is not achieved by the direct pharmacological properties of SSRIs, but by the brain’s compensatory responses that attempt to restore energy homeostasis. These responses take several weeks to develop, which explains why SSRIs have a therapeutic delay. We demonstrate the utility of our claims by examining what happens in animal models of melancholia and during acute and chronic SSRI treatment.
Advancements in pharmacogenomics have introduced an increasing number of opportunities to bring personalized medicine into clinical practice. Understanding how and when to use this technology to guide pharmacotherapy used to treat psychiatric and neurological (neuropsychiatric) conditions remains a challenge for many clinicians. Currently, guidelines exist to assist clinicians in the use of existing genetic information for drug selection and/or dosing for the tricyclic antidepressants, carbamazepine, and phenytoin. Additional language in the product labeling suggests that genetic information may also be useful for determining the starting and target doses, as well as drug interaction potential, for a number of other drugs. In this review, we outline the current status of pharmacogenomic testing for neuropsychiatric drugs as it pertains to information contained in drug labeling, consensus guidelines, and test panels, as well as considerations related to obtaining tests for patients.