Antidepressants relative risks

This herbal product has the most data available to support its usefulness as an antidepressant. Nevertheless, only minimal information is available about its pharmacology and its relative risk-benefit ratio. At least seven different biologically active chemicals have been isolated from crude extracts of hypericum. Several are ubiquitous in the plant kingdom. The exceptions are hypericin and pseudohypericin, which have been assumed to be responsible for any antidepressant activity of this product. Nevertheless, there is the potential for one or more of these seven compounds and their metabolites to mediate desired or undesired effects, particularly when used in combination with other medications (i.e., herb-drug interactions). 

A number of antidepressant drugs, particularly SSRIs, can increase plasma prolactin concentrations, although galactorrhea is uncommon. In a prescription event monitoring survey of about 65 000 patients, compared with SSRIs, moclobemide was associated with a relative risk of galactorrhea of 6.7 (95% Cl = 2.7, 15) (727). However, this was substantially less than the risk associated with the dopamine receptor antagonist risperidone (relative risk compared with SSRIs 32 95% Cl = 14, 70). 

The diagnosis of depression and the use of antidepressant medication are both associated with an increased risk of myocardial infarction. The relative contribution of these two factors is uncertain. In a case-control study of 2247 subjects, taking antidepressants was associated with a 2.2-fold (Cl = 1.3, 3.7) increase in the risk of myocardial infarction (43). This increased risk seemed to be accounted for entirely by the use of tricyclic antidepressants, because selective serotonin re-uptake inhibitors were not associated with an increased risk, although the confidence intervals were wide (relative risk 0.8 Cl = 0.2, 3.5). These findings support the usual clinical advice that... 

The risk of switching into mania, once the patient has emerged from depression, continues to be a factor in treatment considerations. Physicians often choose to discontinue the antidepressant relatively soon after recovery and to continue treatment with the mood stabilizer alone, in order to diminish this risk. This approach is diametrically opposed to the strategies for unipolar depression, where antidepressant treatment must continue at least for 1 year and often longer. 

Kapur, S., Mieczkowski, T., Mann, J. J. (1992, December). Antidepressant medications and the relative risk of suicide attempt and suicide. Journal of the American Medical Association, 268. 3441-3445,... 

Luchins DJ, Oliver AP, Wyatt RJ (1984) Seizures with antidepressants an in vitro teclmique to assess relative risk. Epilepsia 25 25-32. 

Loscher W (2009) Preclinical assessment of proconvulsant drug activity and its relevance for predicting adverse events in humans. Eur J Pharmacol 610 1-11 Luchins DJ, Oliver AP, Wyatt RJ (1984) Seizures with antidepressants an in vitro technique to assess relative risk. Epilepsia 25 25-32... 

Dizziness, vertigo, nausea, vomiting, constipation, and lethargy are all relatively common adverse events. These effects are more pronounced for several days after initiation and following upward dose titration. Seizures have been reported rarely the risk is dose-related and appears to increase with concomitant use of antidepressants, such as tricyclic antidepressants or selective serotonin reuptake inhibitors. Tramadol should be avoided in patients receiving monoamine oxidase (MAO) inhibitors because tramadol inhibits the uptake of norepinephrine and serotonin. 

Non-motor signs of the disorder are also treatable with symptomatic medications. The frequent mood disorder can be treated with standard antidepressants, including tricyclics (such as amitryptiline) or serotonin reuptake inhibitors (SSRIs, such as fluoxetine or sertraline). This treatment is not without risks in these patients, as it may trigger manic episodes or may even precipitate suicide. Anxiety responds to benzodiazepines, as well as to effective treatment of depression. Long-acting benzodiazepines are favored over short-acting ones because of the lesser abuse potential. Some of the behavioral abnormalities may respond to treatment with the neuroleptics as well. The use of atypical neuroleptics, such as clozapine is preferred over the typical neuroleptics as they may help to control dyskinesias with relatively few extrapyramidal side-effects (Ch. 54). 

Side effects, mainly due to serotonin reuptake inhibition include G1 upset, nervousness, and sexual dysfunction. SSRls are associated with an increased risk of falls. Hyponatraemia due to SIADH is an uncommon, but important side effect in elderly patients. Selective serotonin and norepinephrine reuptake inhibitors (S SNRls) such as venlafaxine and duloxetine are also useful in older patients. Other heterocyclic antidepressants of importance in older patients because of relative safety include bupro-prion and mirtazepine. They are reserved for patients with resistance to or intolerance of SSRls. Currently, trazodone is used mostly for sleep disturbance in depression in doses of 50-100 mg at bedtime. The monoamine oxidase inhibitors phenelzine. 

It is difficult to justify, therefore, any use of trazodone in boys, adolescent males, or young men, especially given its relatively limited usefulness as an antidepressant or even a sedative. Even in girls its use is questionable. Nefazodone would appear to be a far better alternative, especially in that it has no recognized sexual side effects, is well tolerated once the patient adapts to the sedative effect, and is not associated with priapism. That is, risks do not include a known increase in priapism above the background incidence (Thompson et ah, 1990 Feiger et ah, 1996 Pecknold and Langer, 1996). 

Continuation of adequate-dose antidepressant medications prevents new episodes in most patients. Discontinuation leads to a significantly greater risk of recurrence for most patients. Maintenance treatment appears to be safe and cost-effective for most patients. These are strong conclusions. Important research questions remain unanswered, but, while striving to address them, it is reassuring to know that we have powerful tools and strategies [Table 20-4) to sustain relative euthymia and effective functioning. Successful treatment of an acute episode of depression is a commendable accomplishment maintenance of euthymia is far more important. 

Buspirone is a partial agonist at serotonin type 1A (5-HTj ) receptors. Unlike benzodiazepines, barbiturates, and alcohol, buspirone does not interact with the GABA receptor or chloride ion channels. Thus, it does not produce sedation, interact with alcohol, impair psychomotor performance, or pose a risk of abuse. There is no cross-tolerance between benzodiazepines and buspirone, so benzodiazepines cannot be abruptly replaced with buspirone. Likewise, buspirone cannot be used to treat alcohol or barbiturate withdrawal and detoxification. Like the antidepressants, buspirone has a relatively slow onset of action. 

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. 

In a re-analysis of antidepressant trial data there was an odds ratio for a suicidal act while taking SSRIs relative to placebo of 2.0 (Cl = 1.2, 3.3), while the risk for completed suicide on SSRIs, although raised, had wide confidence intervals (RR = 3.1 Cl = 0.4, 23.1) (23). One of the author s arguments was that in previous analyses suicidal behaviors occurring during placebo wash-out have been misclassified as happening during placebo treatment. Separation of these two classes of event allows a pro-suicidal effect of SSRIs to be revealed. 

In a matched case-control, primary-care study of over 150 000 patients who received at least one prescription for an antidepressant between 1993 and 1999, in which dosu-lepin was used as the reference standard, there was no relative increased risk of non-fatal self-harm for fluoxetine (OR = 1.16 95% Cl = 0.90,1.50), while the risk for paroxetine approached significance (OR = 29 95% Cl = 0.97, 1.70) (24). The authors suggested that the latter finding might have been due to uncontrolled confounding by severity of depression or apparent suicide risk. In the small number of cases of fatal suicide there was no... 

SSRIs can reportedly cause hyponatremia (SEDA-18, 20 SEDA-26,13). In a case-control study of hyponatremia in 39 071 psychiatric inpatients and outpatients, the incidence of antidepressant-induced hyponatremia was 2.1% (33). SSRI users had a three times higher risk of developing hyponatremia relative to users of other antidepressant drugs (OR = 3.1 95% Cl = 1.3, 8.6). Additional risk factors included older age and concomitant treatment with diuretics. 

Sauer WH, Berlin JA, Kimmel SE. Effect of antidepressants and their relative affinity for the serotonin transporter on the risk of myocardial infarction. Circulation 2003 108 32. 

In an analysis of data from the National Institute of Mental Health Collaborative Depression Study in 643 patients with affective disorders who were followed up after fluoxetine was approved by the FDA in December 1987 for the treatment of depression, nearly 30% (n = 185) took fluoxetine at some point (18). There was an increased rate of suicide attempts before fluoxetine treatment in those who subsequently took fluoxetine. Relative to no treatment, fluoxetine and other antidepressants were associated with non-significant reductions in the likelihood of suicide attempts or completions. Severity of psychopathology was strongly associated with increased risk, and each suicide attempt after admission to the study was associated with a marginally significant increase in the risk of suicidal behavior. The authors concluded that the results did not support the speculation that fluoxetine increases the risk of suicide. 

SODIUM OXYBATE 1. ALCOHOL 2. ANALGESICS - opioids 3. ANTIDEPRESSANTS-TCAs 4. ANTIEPILEPTICS-barbiturates 5. ANTIHISTAMINES 6. ANTIPSYCHOTICS 7. ANXIOLYTICS AND HYPNOTICS-BZDs, buspirone Risk of CNS depression - coma, respiratory depression Additive depression of CNS Avoid co-administration. Caution even with relatively non-sedating antihistamines (cetrizine, desloratidine, fexofenadine, levocetirizine, loratidine, mizolastine) as they can impair the performance of skilled tasks... 

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