Antidepressants, SSRIs

Figure 6.8. Changes that occur following the chronic administration of antidepressants. SSRIs and MAOIs desensitize the inhibitory S-HT a somato dendritic receptors. SSRIs and MAOIs desensitize the inhibitory S-HT b/S-HTid inhibitory auto receptor on the presynaptic terminal. After acute administration, the TCAs and the SSRIs inhibit the uptake of 5-HT into the nerve terminal by binding to the...

Drugs that can increase carbamazepine serum levels include cimetidine, danazol, diltiazem, erythromycin, felbamate, clarithromycin, fluoxetine, isoniazid, niacinamide, propoxyphene, ketaconazole, itraconazole, verapamil, valproate, troleandomycin, loratadine, nicotinamide, tricyclic antidepressants, SSRIs, nefazodone, protease inhibitors. 

Citalopram (Celexa) [Antidepressant/SSRI] WARNING Closely monitor for worsening depression or emergence of suicidality, particularly in pts <24 y Uses Depression Action SSRI Dose Initial 20 mg/d, may t to 40 mg/d X in elderly hqjatic/renal insuff Caution [C, +/-] Hx of mania, Szs pts at risk for suicide Contra MAOI or w/in 14 d of MAOI use Disp Tabs, cap, soln SE Somnolence, insomnia, anxiety, xerostomia, diaphoresis, sexual dysfxn Notes May cause X Na /SIADH Interactions t Effects W/ azole antifungals, cimetidine, Li, macrolides, EtOH t effects OF BBs, carbamazepine, CNS drugs, warfarin X effects W/ carbamaz ine X effects OF phenytoin may cause fatal Rxn W/ MAOIs EMS Use caution w/ CNS depressants, may need a reduced dose concurrent EtOH... 

Long-acting benzodiazepines, tricyclic antidepressants, SSRIs, anti-psychotics... 

TCA, tricyclic antidepressant SSRI, selective serotonin reuptake inhibitor MAOI, monoamine oxidase inhibitor. 0, no effect +, + +, + + + indicate increasing effect. 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

Canada s regulatory agency, Health Canada (2004), followed with a warning to patients of all ages taking the newer antidepressants (SSRIs,... 

The major advantages of SSRIs over the tricyclic antidepressants are their less pronounced anticholinergic adverse effects and lack of severe cardiotoxicity. However, some studies have shown some degree of nervousness or agitation, sleep disturbances, gastrointestinal symptoms, and perhaps sexual adverse effects more commonly in patients treated with SSRIs than in those treated with tricyclic antidepressants. SSRIs may also be associated with an increased risk of suicide, particularly in children under 16 (9). 

Spontaneous reports received by the Netherlands Pharmacovigilance Foundation between 1985 and 1999 have been analysed in a case-control study (15). Relative to other antidepressants, SSRIs were about twice as likely to be implicated in spontaneous reports of extrapyramidal reactions (OR = 2.2 95% Cl = 1.2, 3.9). The risk was greater in patients who were also taking neuroleptic drugs. This result suggests that SSRIs have a modestly increased risk of producing extrapyramidal reactions compared with other antidepressants. However, increased reporting can be influenced by increased awareness. In addition, no account was apparently taken in this study of relative prescription rates of different antidepressants. 

Like other antidepressants, SSRIs are occasionally associated with manic episodes, even in patients with no history of bipolar disorder. Some argue that the affected patients may have had an underlying predisposition to bipolar illness. 

Cardiovascular disease is not a contraindication to lithium, but the risks may be greater, in view of factors such as fluid and electrolyte imbalance and the use of concomitant medications. Close clinical and laboratory monitoring is necessary, and an alternative mood stabilizer may be preferred. While long-term tricyclic antidepressant therapy may be more cardiotoxic than lithium, the newer antidepressants (SSRIs and others) seem to be safe. 

Adverse interactions of lithium with tricyclic antidepressants, SSRIs, and monoamine oxidase inhibitors have been reviewed (581). In reviews of antidepressants and the serotonin syndrome, a possible contributory role has been suggested for lithium, based on case reports with tricyclic antidepressants, SSRIs, trazodone, and venlafax-ine (204,582). 

PROCAINAMIDE ANTIDEPRESSANTS-SSRIs SSRIs may t procainamide levels SSRIs inhibit CYP2D6-mediated metabolism of procainamide Monitor PR and BP closely watch for procainamide toxicity... 

CILOSTAZOL ANTIDEPRESSANTS-SSRIs Fluoxetine, fluvoxamine and sertraline t cilostazol levels Fluoxetine, fluvoxamine and sertraline inhibit CYP3A4-mediated metabolism of cilostazol Avoid co-administration... 

EFAVIRENZ ANTIDEPRESSANTS-SSRIs 1. Possible t efficacy and t adverse effects, including serotonin syndrome, with fluoxetine 2. Possible i efficacy with sertraline 1. Uncertain mechanism possibly t bioavailability 2. CYP2B6 contributes most to the demethylation of sertraline with lesser contributions from CYP2C19, CYP2C9, CYP3A4 and CYP2D6 1. Use with caution consider i dose of fluoxetine 2. Watch for therapeutic failure, and advise patients to report persistence or lack of improvement of symptoms of depression, t dose of sertraline as required, titrating to clinical response... 

Masand PS, Gupta S. Long-term side effects of newer-generation antidepressants SSRIS, venlafaxine, nefazodone, bupropion, and mirtazapine. Ann Clin Psychiatry 2002 14 175-82. 

A delayed response in GAD is not as critical as with acute situational anxiety. A sensible approach (especially in benzodiazepine naive patients) is to start with buspirone for 6-8 weeks, at least 30 mg day increasing over 2-3 weeks to minimise unwanted actions patients should be warned not to expect an immediate benefit. Those who do not respond should receive an antidepressant (SSRI or venlafaxine) for 6-8 weeks at full therapeutic dose. There remain some patients, including those with a... 

Erectile dysfunction (ED), the inability to achieve or maintain a penile erection sufficient to permit satisfactory sexual intercourse, is estimated to affect over 100 million men worldwide, with a prevalence of 39% in those of 40 years. Its numerous causes include cardiovascular disease, diabetes mellitus and other endocrine disorders, alcohol and substance abuse, and psychological factors (14%). While the evidence is not conclusive, drug therapy is thought to underlie 25% of cases, notably from antidepressants (SSRI and tricyclic), phenothiazines, cypro-terone acetate, fibrates, levodopa, histamine H -receptor blockers, phenytoin, carbamazepine, allopurinol, indomethacin, and possibly adrenoceptor blockers and thiazide diuretics. 

Although certain illnesses contribute to falls, medications have been shown to cause falls independent of other factors. The most commonly offending drugs are benzodiazepines because they have been shown to increase falls and hip fractures. An association between the dose (the higher the dose, the more likely the fall), duration of use, and type of benzodiazepine (e.g., long-acting medications) has also been reported. Other classes of medications that increase the risk of falls include tricyclic antidepressants, SSRIs, and opioid analgesics. 

Antidepressants SSRI (citamlopram, fluvoxamine, fluoxetine, sertraline, paroxetine)... 

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