Agitated depression serotonin

I believe that people who suffer from an agitated depression—marked by feelings of anger, irritability, or excess energy—are responding to an imbalance that includes too little serotonin and too much norepi/dopa. 

Western brain chemistry connection When depressed, likely to be diagnosed with agitated depression or excess of dopamine in relation to serotonin may be helped by dietary and exercise recommendations for excess dopamine and serotonin deficiency ... 

Selected for clinical trials as a compound to calm agitated patients, imipramine was relatively ineffective. However, it was observed to be effective in the treatment of certain depressed patients (38). Early studies on the mechanism of action showed that imipramine potentiates the effects of the catecholamines, primarily norepinephrine. This finding, along with other evidence, led to the hypothesis that the compound exerts its antidepressant effects by elevating norepinephrine levels at central adrenergic synapses. Subsequent studies have shown that the compound is a potent inhibitor of norepinephrine reuptake and, to a lesser extent, the uptake of serotonin, thus fitting the hypothesis that had been developed to explain the antidepressant actions ofMAOIs. 

Serotonin-Boosting Antidepressants. Antidepressants that enhance serotonin activity in the brain have also been studied in ADHD. In particular, fluoxetine (Prozac) and the serotonin-selective TCA clomipramine (Anafranil) have been the most extensively evaluated, with mixed success. They provide some benefit for aggression and impulsivity but don t significantly improve the poor attention of ADHD. As a result, the SSRls and other serotonin-boosting antidepressants do not appear to be effective first-line treatments for ADHD. Conversely, depressed patients without ADHD often show improvements in symptoms of concentration and attention when treated with a SSRI. Although SSRls are not widely used in the treatment of ADHD, they may be worthy of consideration in ADHD patients whose impulsivity is not controlled by stimulants alone. Those with comorbid conduct disorder or ODD who are prone to agitation and at times violent outbursts may be helped by the addition of a SSRI. 

Uses Obesity Action Blocks uptake of norepinephrine, serotonin, dopamine Dose 10 mg/d PO, may to 5 mg after 4 wk Caution [C, -] w/ SSRIs, Li, dextromethorphan, opioids Contra MAOI w/in 14 d, uncontrolled HTN, arrhythmias Disp Caps SE HA, insomnia, xerostomia, constipation, rhinitis, tach, HTN Interactions T Risk of serotonin synd W/ dextromethorphan, ergots, fentanyl, Li, meperidine, MAOIs, naratriptan, pentazocine, rizatriptan, sumatriptan, SSRIs, tryptophan, zolmitriptan, St. John s wort effects W/ cimetidine, erythromycin, ketoconazole T CNS depression W/ EtOH EMS Use fentanyl w/ caution, may T risk of serotonin synd concurrent EtOH use can T CNS depression OD May cause tach, HTN, diaphoresis, HA, fever, agitation, muscle tremors, and Szs symptomatic and supportive... 

Perhaps the most commonly used example of the serotonin 2A strategy is the combination of an SSRI with trazodone. Clinicians have long recognized that trazodone will improve the agitation and insomnia often associated with SSRIs, allow high doses of the SSRI to be given, and consequently boost the efficacy of the SSRI not only in depression, but also in obsessive-compulsive disorder and other anxiety disorders. Thus, both types of bad math are in play here. 

Fawcett et al. proposed four hypothetical pathways leading to suicide in clinical depression an acute pathway involving severe anxiety/agitation associated with high brain corticotrophin-releasing factor levels, trait baseline and reactivity hopelessness, severe anhedonia, and trait impulsiveness associated with low brain serotonin turnover, with low total cholesterol as a... 

A 23-year-old Japanese woman with major depression took a single dose of paroxetine (20 mg) and 1 hour later had agitation, myoclonus, mild hyperthermia (37.5°C), sweating, and diarrhea, symptoms that meet the criteria for the serotonin syndrome she recovered with supportive treatment over 3 days (2). 

Researchers have discovered that there are two types of monoamine oxidase enzyme MAO-A and MAO-B, each located in different regions of the body. Older MAOIs, such as Nardil, inhibit both versions of monoamine oxidase, resulting in increased serotonin and norepinephrine inside the cell (and also leakage into the synapse, thus activating receptors). Increases in serotonin and noreinephrine receptor activation can lead to several over-stimulating side effects. These central nervous system effects include tremors, insomnia, agitation, and occasionally, precipitation of a mania in patients with bipolar depression. 

Bupropion (100 mg p.o. b.i.d.) is indicated in the treatment of depression. It is reserved for patients who cannot tolerate or have not responded to other medications. Bupropion does not alter the uptake of serotonin, has an equivocal effect on the uptake of norepinephrine, but blocks the uptake of dopamine. Bupropion has no affinity for alpha-1 and alpha-2-adrenergic receptors, H,-histamine receptors, muscarinic cholinergic receptors, or D2-dopaminergic receptors. It does not cause sedation or orthostatic hypotension. However, because it is structurally related to amphetamine, it may cause insomnia, agitation, and anxiety shortly after initiation of therapy. Bupropion lowers the seizure threshold and hence is contraindicated in patients with a history of seizure disorder (see also Tables 5 through 7). 

Another risk of antidepressants in vulnerable patients (particularly those with unrecognized bipolar depression) is switching, sometimes suddenly, from depression to hypomanic or manic excitement, or mixed, dysphoric-agitated, manic-depressive states. To some extent this effect is dose-related and is somewhat more likely in adults treated with tricyclic antidepressants than with serotonin reuptake inhibitors, bupropion, and perhaps with MAO inhibitors. Risk of mania with newer sedating antidepressants, including nefazodone and mirtazapine, also may be relatively low, but some risk of inducing mania can be expected with any treatment that elevates mood, including in children with unsuspected bipolar disorder. 

Fewer adverse effects were reported among moclobemide-treated patients compared with selective serotonin reuptake inhibitor (SSRI)-treated patients. Since moclobemide does not induce orthostatic hypotension, does not possess anticholinergic properties, and is not cardiotoxic, it is very well suited among the MAOIs for the treatment of depression. Moclobemide has limited potential to elicit a hypertensive crisis, because the pressor effect of tyramine from food is only marginally potentiated compared with tranylcypromine. The pressor effect of tyramine is normalized within 3 days of cessation of treatment with moclobemide. The combination of SSRIs and moclobemide has good efficacy in cases of refractory depression, but there is controversy as to whether toxic side-effects such as serotonin syndrome can result from this combination. Currently, more studies are needed before this combination can be recommended. Acute overdose with MAOIs causes agitation, hallucinations, hyperpyrexia, hyperreflexia, convulsions, and death. The most dangerous MAOIs in overdose are the irreversible non-selective MAOIs. T2s-27... 

Tranylcypromine (Parnate) Blocks metabolisni of biogenic amines (norepinephrine, serotonin, dopamine) increasing the synaptic concentration of these transmiTters. Suppresses REM sleep. Used tu tiedt depression if tricyclic antidepressants fail and when electroconvulsive therapy fails or is refused. Also used to treat narcolepsy, phobic/anxiety states and Parkinson s disease. Hepatotoxicity, excessive CNS stimulation, orthostatic hypoten -sion. Overdose may cause agitation, hallucinations, hyperreflexia, hyperpyrexia, convulsions, altered blood pressure. ... 

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