Suicidality from TCAs

Of greater concern is the safety of the TCAs. Toxic levels of these medications can produce lethal cardiac arrhythmias, seizures, and suppression of breathing. An overdose of a 1-2 week supply of most TCAs is often fatal, a serious consideration when prescribing medication to depressed patients with suicidal thoughts. Children taking imipramine for treatment of ADHD have died from sudden cardiac death consequently, child psychiatrists seldom use TCAs. Likewise, patients with heart disease or seizure disorders are more likely to have dangerous complications from TCAs and should avoid them. 

In addition to a different side-effect profile, SSRIs differ from TCAs by virtue of their wider safety margin, because they do not cause life-threatening toxic effects (e.g., patients having survived acute ingestion of amounts equal to 10 times the daily dose) (434). For this reason, many clinicians prefer these drugs in patients who may be a significant suicide risk. 

Overdose. Depression is a risk factor for both parasuicide and completed suicide, and TCAs are commonly taken by those who deliberately self-harm. Dothiepin (dosulepin) and amitriptyline are particularly toxic in overdose, being responsible for up to 300 deaths per year in the UK despite the many alternative antidepressants that are available. Lofepramine is at least 15 times less likely to cause death from overdose clomipramine and imipramine occupy intermediate positions. 

Imipramine (Tofranil) [Antidepressant/TCA] WARNING Close observation for suicidal thinking or unusual changes in behavior Uses Depres-sion, enuresis, panic attack, chronic pain Action TCA t CNS synaptic serotonin or norepinephrine Dose Adults. Hospitalized Initial 100 mg/24 h PO in doses T over several wk 300 mg/d max Output Maint 50-150 mg PO hs, 300 mg/24 h max Peds. Antidepressant 1.5-5 mg/kg/24 h daUy-qid Enuresis >6 y 10-25 mg PO qhs T by 10-25 mg at 1-2-wk int vals (max 50 mg for 6-12 y, 75 mg for >12 y) Rx for 2-3 mo, then tap Caution [D, /-] Contra Use w/ MAOIs, NAG, acute recovery from MI, PRG, CHF, angina, CVD, arrhythmias Disp Tabs, caps SE CV Sxs, dizziness, xerostomia, discolored urine Interactions t Effects W/ amiodarone, anticholinergics, BBs, cimetidine, diltiazem, Li, OCPs, quinidine, phenothiazines, ritonavir, verapamil, EtOH, evening primrose oil t effects OF CNS depressants, hypoglycemics, warfarin T risk of serotonin synd W/MAOIs 4-... 

The most beneficial action of TCAs is their ability to block serotonin (5-HT) and norepinephrine (NE) uptake. TCAs are shaped so that they lock onto specific uptake transporters, the enzymes that clear neurotransmitters from the synapse (the space between neurons). As discussed in Chapter 1, serotonin is a neurotransmitter that has been shown important for mood regulation. For instance, decreased levels of serotonin receptors have been found in suicide victims who died violent deaths. Norepinephrine is another neurotransmitter important in depression, but more associated with the brain s reactions to stress. Once the neurotransmitter uptake transporters are bound by TCAs, serotonin and norepinephrine levels begin to build up inside the synapse. The longer serotonin and norepinephrine stay in the synapse, the more often the receptors are activated. Receptor activation causes negative feedback loops to adjust the overall amount of transporters and receptors. This feedback adjustment can take several weeks, which is why depression doesn t go into remission until a few weeks pass. 

---