Suicide with tricyclic antidepressants

Apart from symptomatic, general measures (gastric lavage, cooling with ice water), therapy of severe atropine intoxication includes the administration of the indirect parasympathomimetic physostigmine (p. 102). The most common instances of atropine" intoxication are observed after ingestion of the berry-like fruits of belladonna (children) or intentional overdosage with tricyclic antidepressants in attempted suicide. 

In a prospective cohort study of over 450 patients who had attempted suicide by antidepressant ingestion the risk of seizures after venlafaxine overdose (14%) was significantly greater than that of SSRIs (1.3%) and similar to that seen with dosulepin (11%) (12). Rates of 5HT toxicity did not differ significantly between venlafaxine and SSRIs (29% versus 19%) but were greater than with tricyclic antidepressants (1.2%). Unlike SSRIs, venlafaxine was associated with significant prolongation of the QT interval tricyclic antidepressants had a similar effect. 

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). 

Furthermore, a meta-analysis of controlled trials did not point to a greater risk of suicide attempts or suicidal ideation with fluoxetine than with tricyclic antidepressants (1). 

Suicidal ideation has been described after 2-7 weeks of fluoxetine (17) and other case reports (SEDA-16, 9) (SEDA-17, 19). A causal link was initially questioned (SED-12, 57) (SEDA-15, 15) (SEDA-17, 19), and in one controlled trial there was no increase (SEDA-16, 9). Furthermore, a meta-analysis of controlled trials did not point to a greater risk of suicide attempts or suicidal ideation with fluoxetine than with tricyclic antidepressants (1). 

Toxic Effects of Acute Overdoses Acute poisoning with tricyclic antidepressants or MAO inhibitors is potentially hfe-threatening. Fatalities are much less common since modern antidepressants have widely replaced these drugs however, suicide rates have not declined consistently as clinical usage of modern antidepressants has increased. Deaths have been reported with acute doses of 2 g of imipramine, and severe intoxication can be expected at doses >1 g, or about a week s supply. If a patient is severely depressed, potentially suicidal, impulsive, or has a history of substance abuse, prescribing a relatively safe antidepressant agent with close clinical follow-up is appropriate. If a potentially lethal agent is prescribed, it is best dispensed in small, sublethal quantities, with the risk that sustained adherence to recommended treatment may be compromised. 

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). 

Tricyclic Antidepressants (TCAs). Because of their effectiveness not only for depression but for anxiety disorders such as panic disorder as well, TCAs were the first medications formally tested in the treatment of PTSD. Three TCAs, amitriptyline, imipramine, and desipramine, have been studied in small trials, producing modest benefit for reexperiencing and hyperarousal symptoms, without any relief of avoidance/numbing symptoms. Given this limited benefit in conjunction with the side effect burden and potential for toxicity in a suicide prone population, TCAs are infrequently used in the treatment of PTSD. Please refer to Chapter 3 for more information regarding TCAs. 

The excellent clinical efficacy of the TCAs has been well documented and the pharmacokinetic profiles are favourable. The most serious disadvantage of the TCAs lies in their cardiotoxicity. Thus, with the exception of lofepramine, all the tricyclic antidepressants, including maprotiline, block the fast sodium channels in the heart which can lead to heart block and death. Approximately 15% of all patients with major depression die by suicide and a high proportion of these (up to 25%) do so by taking an overdose of TCAs. Such a dose can be as low as 5-10 times the recommended daily dose. 

Tricyclic antidepressants are cardiotoxic, inducing tachycardias and an increased tendency for ventricular arrhythmias with high doses. This dose dependent cardiotoxicity gives these agents a low therapeutic index. Overdoses are characterized by cardiac conduction disturbances, hyperpyrexia, hypertension, confusion, hallucinations, seizures and coma and there is a high mortality rate in suicide attempts. Depressed patients should therefore not be given more than one week supply of these drugs. 

Tricyclic antidepressants are still prescribed today, but some patients experience side effects such as dry mouth, blurry vision, constipation, and other uncomfortable conditions. Other antidepressants have since been found that induce fewer side effects. One of the most popular is fluoxetine, which is marketed under the trade name Prozac. This drug, along with Zoloft and other antidepressants, are known to inhibit reuptake proteins specifically for serotonin. As a result, these drugs are called selective serotonin reuptake inhibitors, or SSRIs. Although some concerns have appeared because of a possible risk of suicide in young patients who take Prozac, these drugs are commonly prescribed and have proved highly effective in millions of patients. 

Atropineintoxication is potentially lethal in children (see Chapter 8) and may cause prolonged severe behavioral disturbances and arrhythmias in adults. The tricyclic antidepressants, when taken in overdosage (often with suicidal... 

Precautions The tricyclic antidepressants should be used with caution in manic-depressive patients, since they may unmask manic behavior. The tricyclic antidepressants have a narrow therapeutic index for example, 5 to 6 times the maximal daily dose of imipramine can be lethal. Depressed patients who are suicidal should be given only limited quantities of these drugs and should be monitored closely. Drug interactions with the tricyclic antidepressants are shown in Figure 12.5. 

Fergusson et al. (2005) searched the literature and found 702 randomized clinical trials (87,650 patients) comparing SSRIs with either placebo or an active non-SSRI control medication. They found a statistically significant, more than two-fold increased risk of suicide attempts on SSRIs compared to placebo. The odds ratio of suicide attempts in SSRI-treated patients versus placebo patients was 2.28 (p = 0.02) and a 95% confidence interval (Cl) of 1.14-4.55. They also found an increased suicide risk between SSRIs and other medications, excluding tricyclic antidepressants. There was no difference between the SSRIs and tricyclics in suicide risk. Overall, their results documented an association between suicide attempts and the use of SSRIs. ... 

There is no substantial published evidence that any antidepressants, new or old, ameliorate suicidal tendencies. Instead, there is clinical evidence that the tricyclic antidepressants, like the SSRIs, can cause suicide. Baldes-sarini (1978) warned, The risk of suicide may even increase with initial improvement, since activity usually increases before mood elevation. Baldessarini s explanation for drug-induced suicidality, formulated many years ago, is oversimplified but the observation remains correct, that antidepressants cause suicidality, especially early in treatment or during dose changes. 

Some of the tricyclic antidepressants and barbiturates are probably more lethal than BZs taken alone. But when BZs are combined with other drugs, such as alcohol, their lethality is increased. Overall, the BZs account for many more suicides than most physicians probably realize. 

Suicidal ideation of some kind almost invariably accompanies severe depression. Hence the relative toxicity of antidepressants in overdose can be important in determining treatment choice. It is accepted that SSRIs are less dangerous in overdose than tricyclic antidepressants, but there are fewer data on the toxicity of other antidepressants. The presentation and likely toxicity in overdose of several newer antidepressant drugs have been reviewed (9). Deaths in overdose have been most clearly associated with amfebutamone and venlafaxine. 

Educational policies and commercial marketing of antidepressant drugs have led to an increase in the detection and treatment of depression. Conceivably this may be associated with the fall in suicide rates noted in Finland. However, overdosage of tricyclic antidepressants continues to contribute to deaths from suicide. Whether completely replacing tricyclics with less toxic compounds would lower overall suicide rate remains controversial. 

Paracetamol plus dextropropoxyphene, the combination known as co-proxamol, is available as a prescription-only analgesic in many countries. Self-poisoning can be lethal, as respiratory depression can occur from an excessive dose of dextropropoxyphene. In England and Wales, co-proxamol alone accounts for 5% of all suicides, and overdose is more likely to result in death than overdose with paracetamol alone or tricyclic antidepressants (81). Furthermore, although it is often prescribed, it is no more effective than paracetamol for short-term relief of pain. It should not be prescribed without good... 

Major depression is a common psychiatric illness associated with significant morbidity [25]. The illness is usually episodic and manifests with a depressed mood reduced energy changes in appetite, sleep, and concentration and psychological symptoms, such as reduced self-esteem and suicidal ideation. As many as 10% of people may experience a depressive episode at some point in their lives, with women more commonly affected than men. Despite its frequency, more than half of the patients with this illness remain untreated [26]. Unfortunately, the longer the duration of the illness, the poorer the outcome, with an increased rate of recurrence [27]. Effective treatment for depression has been available for nearly two generations. Older medications, the tricyclic antidepressants and... 

The client with major depressive disorder is suicidal. The client was prescribed the tricyclic antidepressant imipramine (Tofranil) 3 weeks ago. Which priority intervention should the nurse implement ... 

Tricyclic antidepressants are commoniy taken in overdose by suicidal patients and represent a major cause of poisoning hospitaiizations and deaths. Currently available tricyclic antidepressants are described in Table 11-7. Amitriptyline is also marketed in combination with chlordiazepoxide (Limbitrol ) or perphenazine (Etrafon or Tria-viF ). Cyclobenzaprine (FlexerilTW), a centrally acting muscle relaxant (see p 339), is structurally related to the tricyclic antidepressants but exhibits minimal cardiotoxic and variable CNS effects. Newer, noncyclic antidepressants are discussed on p 88. Monoamine oxidase inhibitors are discussed on page 269. 

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