Depression
Henry J. Woodford in Essential Geriatrics, 2022
The majority of antidepressants are believed to act by potentiating the effects of serotonin and/or norepinephrine within the brain. There is insufficient evidence to reliably compare all of the available antidepressant medications with one another. Meta-analyses suggest that the differences in efficacy and adverse events between serotonin specific reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and atypical agents may only be small.24 However, a review of studies performed in primary care suggested that SSRIs are better tolerated than TCAs.25 The decision on which agent to choose may be based on adverse effect profiles (seeTable 8.1). Those with more anticholinergic properties (e.g. TCAs; see page 47) are usually best avoided in older people. Another factor is whether it would be beneficial to stimulate or sedate the patient, depending on presenting symptoms. Those with insomnia may benefit from a sedating drug such as mirtazapine at night, whereas those with lethargy or withdrawal may be more suited to a non-sedating drug such as sertraline.
Physical activity and mental health
Joe Piggin, Louise Mansfield, Mike Weed in Routledge Handbook of Physical Activity Policy and Practice, 2018
Much of the understanding behind the biological mechanisms that may improve depression symptoms stems from a knowledge of the pharmacodynamic effects of antidepressant medications (Nutt 2008). The most common types of antidepressants are serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), which primarily increase the amount of serotonin in the brain, an important chemical for mood regulation. Similar to these medications exercise has also been shown to increase serotonin availability, which may explain its anti-depressant effects. It is well established that in animals, an acute bout of exercise is consistently shown to increase both hippocampal (a key brain region in depression) (Meeusen et al. 1996; Wilson & Marsden 1996) and whole brain serotonin concentration (see Meeusen & De Meirleir 1995). In humans where directly measuring serotonin in the brain is not possible, acute bouts of exercise increase free tryptophan (the amino acid precursor of serotonin) in the blood, which is a marker of serotonin production in the brain (Melancon, Lorrain, & Dionne 2012; Nybo et al. 2003). Additionally, exercise also seems to increase the availability of norepinephrine and dopamine, which are other neurotransmitters that have been implicated in depression (Alsuwaidan et al. 2009). Overall, it seems that exercise, like antidepressants, tends to increase the amount of serotonin available and other mood regulating neurotransmitters, which may be one way that exercise improves depression symptoms.
Examples from Actual Clinical Trials in Choosing and Specifying Estimands
Craig Mallinckrodt, Geert Molenberghs, Ilya Lipkovich, Bohdana Ratitch in Estimands, Estimators and Sensitivity Analysis in Clinical Trials, 2019
MDD is a common psychiatric condition with a lifetime incidence of approximately 15% (Kessler et al., 2005). The disorder ranges from mild to severe and is associated with significant potential morbidity and mortality, contributing to suicide and adverse impact on concomitant medical illnesses, interpersonal relationships, and work. The objectives of treatment are to reduce or resolve signs and symptoms of the disease, restore psychosocial and occupational function, and reduce the likelihood of relapse or recurrence (Primary Care Clinical Practice Guideline, 2010). Guidelines support pharmacological therapy for the treatment of depression in addition to psychotherapy. Antidepressant medications include selective serotonin reuptake inhibitors (SSRIs), serotonin/norepinephrine reuptake inhibitors (SNRIs), atypical antidepressants, serotonin-dopamine activity modulators (SDAMs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs) (Practice Guideline for The Treatment of Patients With Major Depressive Disorder, 2010).
Cytogenotoxic effects of venlafaxine hydrochloride on cultured human peripheral blood lymphocytes
Published in Drug and Chemical Toxicology, 2020
Selim Ayabaktı, Ayşe Yavuz Kocaman
Antidepressants are drugs that are used to alleviate the symptoms of depression since 1950 around the world (Draz et al.2009). The prescription of antidepressants has been increasing in recent years (Attia and Bakheet 2013). According to the WHO (2012), depression is estimated to affect 350 million people worldwide. Reddy (2012) reported that depression will be the second leading cause of the burden of disease by 2020 and the first by 2040. In addition to their widespread use, antidepressants are long-term drugs used by patients (Brambilla et al.2009) and, therefore, should be considered for their adverse effects on humans’ health. In previous studies, many antidepressants have been found genotoxic, mutagenic, and cytotoxic in various test systems (Attia and Bakheet 2013, Donbak et al.2014, Lacaze et al.2015, Madrigal-Bujaidar et al.2015, Silva et al.2016, Elmorsy et al.2017, Yilmaz et al.2017, Cobanoglu et al.2018). In addition, there are experimental and epidemiological studies indicating that antidepressants promote tumor formation in animals, and there is a correlation between their use and cancer risk (Cotterchio et al.2000, Steingart et al.2003, Cosgrove et al.2011).
Anti-depressant effects of ethanol extract from Cannabis sativa (hemp) seed in chlorpromazine-induced Drosophila melanogaster depression model
Published in Pharmaceutical Biology, 2021
Yejin Ahn, Sung Hee Han, Min Guk Kim, Ki-Bae Hong, Woo Jung Kim, Hyung Joo Suh, Kyungae Jo
Anti-depressants typically work by blocking the reuptake of certain neurotransmitters (norepinephrine, serotonin, and dopamine) to the post-synaptic neuron. Anti-depressants that are mainly used are monoamine oxidase inhibitors which improve the function of monoamine transporters, and tricyclics that increase the levels of norepinephrine and serotonin (Thanacoody 2020). Recently, selective serotonin reuptake inhibitors, such as fluoxetine (Prozac), which selectively act on the serotonin system, are being used (Kumar and Sharma 2020). However, these medications have shown negative side effects, such as sexual dysfunction, vomiting, diarrhoea, constipation, gastrointestinal disorders, loss of appetite, dry mouth, anxiety, and insomnia (Ries et al. 2017). Therefore, many people are seeking naturally derived anti-depressants.
Pharmacological management of agitation among individuals with moderate to severe acquired brain injury: A systematic review
Published in Brain Injury, 2018
Swati Mehta, Amanda McIntyre, Shannon Janzen, Jerome Iruthayarajah, Ali Bateman, Robert Teasell
Antidepressants modulate neurotransmitters involved in behavioural disorders including serotonin, dopamine, and norepinephrine (4). For example, serotonin-reuptake inhibitors (SSRIs) prevent the presynaptic neuron from removing serotonin from the synapse, thereby increasing the time and quantity of serotonin in the synaptic cleft, which then aids in regulating emotions such as impulse aggression (33). Tricyclic antidepressants (TCAs) act via a different cellular mechanism to increase the quantity of serotonin and norepinephrine in the synaptic cleft to achieve similar emotional effects. Dopamine and norepinephrine also play a role in cognitive functioning and are specifically implicated in diverse processes such as memory, attention, learning, processing speed, and executive function (34).
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