| Examples of SSRI-type antidepressant drugs: | Paroxetine, fluvoxamine,citalopram, escitalopram, sertraline, fluoxetine. |
| Advantages of SSRIs compared to earlier generation antidepressants, especially tricyclic antidepressants (TCAs): |
Reduced lethality in overdose compared to TCAs; reduced significant cardiovascular and anticholinergic (antimuscarinic) side effects. Citalopram is notable in that QT prolongation is a concern under some dosing regimens and should only be used cautiously in those patients at risk for cardiac rhythm disorders. |
| Some examples of atypical-type antidepressants: | Buproprion is one example in this agent may ask through the dopamine neurotransmitter system. Agents that inhibit both serotonin and norepinephrine reuptake include venlafaxine and duloxetine. Nefazodone not only inhibits serotonin reuptake but also inhibits the 5-HT2 postsynaptic receptor. Vilazodone is both a partial agonist that 5-HT1A postsynaptic sites as well as a serotonin reuptake inhibitor. Mirtazapine (Remeron) promotes both noradrenergic and serotonergic neurotransmission while selectively inhibiting presynaptic
α-2 adrenergic receptors. |
| Effectiveness of typical and atypical antidepressants in management of major depressive disorders: |
Both atypical and typical antidepressant agents appear efficacious. |
| Examples of SSRI medical uses other than for management of major depressive disorder: |
Bulimia, generalized anxiety disorder, obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD) and panic attack treatment. |
| Duloxetine and pain management: | Duloxetine may be effective in treating diabetic peripheral neuropathy and fibromyalgia. |
| Venlafaxine in pain management: | Venlafaxine may be helpful in management of neuropathic pain. |
| Examples of SSRIs or atypical agents that tend to be sedating: |
Sedation is most likely seen with paroxetine, fluvoxamine and mirtazapine administration, although most medications in the SSRI and atypical group are "activating" and may be given in the morning to avoid interfering sleep. |
| Delay in clinical response associated with antidepressant administration: | Just as an example: fluoxetine may require from 2 to 6 weeks to exhibit efficacy in management of depression; 4-8 weeks to exhibit efficacy in treating panic disorder and from 6-12 weeks in treating OCD. |
| Side effects associated with SSRI/atypical antidepressant medications: |
Headache, nausea, insomnia, nervousness, tinnitus are not uncommon. Akathisia (inner restlessness) is not uncommon with SSRIs, although other extrapyramidal symptoms
occur infrequently. Sexual side effects associated with SSRIs include erectile dysfunction, retrograde ejaculation and dysorgasmia. Erectile dysfunction may be improved in some patients through the use of oral phosphodiesterase-5 antagonists including sildenafil, tadalafil, or vardenafil. Restoring erectile function may also be
accomplished by adding buproprion to the drug regimen. Drug-induced anorgasmia may be improved by cyproheptadine administration. |
| SSRIs and "serotonin syndrome": | SSRIs are effective serotonin reuptake antagonists and as such either alone
at high dosage or in combination with, for example MAO inhibitors, induce serotonin syndrome. The list of MAOIs that in combination with SSRIs predispose the serotonin syndrom include the antiparkinsonian drug, selegiline. Serotonin syndrome may present with rigidity, autonomic instability, hyperthermia, confusion, delirium, myoclonus and coma. |
| Withdrawal symptoms with SSRIs: | SSRIs along with venlafaxine may be associated with withdrawal symptoms that present as dysphoric mood, flu-like symptoms and agitation. |
| Fetal malformations and SSRI/atypical agents: | Administration of sertraline, fluvoxamine, citalopram, venlafaxine, and fluoxetine may
increase the risk of fetal malformation when administered during pregnancy. The absolute risk of congenital defects in this setting may be low, however. The clinical question concerning use of SSRIs or other psychoactive drugs during pregnancy and postpartum requires an individualized decision, following careful assessment of risk-benefit considerations. |
| Venlafaxine side effects: | The major side effects include nervousness, nausea and significant sweating. Dose-related hypertension may occur in some patients. |
| Duloxetine side effects: |
Side effects with duloxetine include not only dizziness, dry mouth and fatigue but also possible small increases in blood pressure. Inhibitors of the cytochrome P450 isoforms CYP1A2 and CYP2D6 may result in increased duloxetine serum levels along with increased toxicity risk. |
| Nefazodone and special concerns for toxicities: | Although nefazodone does not exhibit anticholinergic characteristics of TCAs or agitation of the type that occasionally occurs with SSRIs, there are important drug-drug interactions involving nefazodone. Specifically, nefazodone
should not be used with terfenadine, astemizole, or cisapride. As a result of nefazodone-mediated inhibition of the cytochrome P450 CYP3A4 isoform,
use of the above medications can result in significant and dangerous QT
prolongation along with ventricular tachycardia or death. Following nefazodone-mediated cytochrome P450 isoform inhibition, cyclosporine levels may increase 6-10 times. |
| Mirtazapine and side effects: | Mirtazapine enhances both serotonergic and noradrenergic activity and exhibits
fewer sexual side effects compared with SSRIs. Sedating effects due to mirtazapine-mediated histamine receptor antagonism makes this medication a reasonable choice for patients who exhibit both depression and insomnia. Antagonism at the 5-HT3 receptor by mirtazapine results in the agent being
an effective antiemetic. |
| Mirtazapine-most common adverse side effects: | Increased appetite, weight gain, dizziness, lipid abnormalities and somnolence. |
| Non-depression use for tricyclic antidepressants (TCAs): | Panic disorder, pain syndromes, anxiety. Clomipramine appears effective in
obsessive-compulsive disorder management. Imipramine appears useful in managing enuresis. Amoxapine may be helpful in treating psychotic depression. Desipramine may be useful in reducing cocaine withdrawal craving. |
| TCAs and neurotransmitter systems: | In general, TCAs antagonize reuptake in both serotonergic and noradrenergic (norepinephrine) systems. |