Tricyclic antidepressants
An earlier family of antidepressants that was once often used to treat depression is represented by the tricyclic antidepressants. Their three-ring chemical structures are referred to be tricyclic. This handout will refer to the tricyclic antidepressants as TCAs for simplicity. These agents have been replaced with more recent equivalent in efficacy to antidepressants but safer and with fewer side effects. They continue to be used for treating
depression, although these drugs are more often used to treat illnesses other than those for which they are authorized, such chronic pain syndromes, eating disorders, panic disorder, generalized anxiety disorder, and insomnia, premenstrual dysphoric disorder and bulimia nervosa). The labeled use of a drug refers to using it as prescribed.
The pharmacological effects and structural similarities among TCAs are noteworthy. These drugs presumably function by preventing serotonin and norepinephrine, two crucial neurotransmitters in the central nervous system, from being reabsorbed into brain cells. Neurotransmitters are substances generated by neurons in the brain that allow neurons to interact with one another. Examples of these neurotransmitters include serotonin and norepinephrine. One neuron releases the neurotransmitters into the space between it and the subsequent neuron. The neurotransmitters interact with receptors, which are particular locations on the surface membrane of neurons.
Mechanism of action
The chemical signal is then converted into an electrical impulse, which passes through the cell and releases further neurotransmitters. Along a chain of neurons, this neurotransmission process is repeated. Following the release of neurotransmitters and the transport of the chemical signal to Reuptake is the process by which neurotransmitters are taken up by nearby neurons and reabsorbed into brain tissue.
The antidepressant may increase the neurotransmitter’s effects by preventing the neurotransmitters from returning to the neurons from whence they were emitted.
The reuptake actions of the TCAs differ based on their molecular structure. While some drugs primarily inhibit serotonin reuptake, others may have a comparatively stronger norepinephrine reuptake blocking effect. However, the majority of TCAs partially or completely impede the reuptake of norepinephrine and serotonin.
Certain neurotransmitters may be unusually low in the brain, which may lead to depression and other mental illnesses. This anomaly may subsequently lead to alterations in the impacted brain regions, leading in psychiatric signs like anxiousness or sadness. The antidepressant’s enhancement of neurotransmission returns damaged brain regions to normal function, lessening the illness’s symptoms.
Typical Side Effects
Some people may find it intolerable to take TCAs due to their various negative effects. The effectiveness of these medications is often limited by side effects, particularly when doses are greater. Sometimes, lowering the dose or gradually increasing it will help control side effects. Because drug blood levels may identify patients with excessively high levels when toxic effects are suspected or those with low levels of drug in whom lack of absorption or rapid metabolism is suspected, monitoring blood drug levels for a particular TCA can also help ensure the greatest benefit with the fewest side effects.
The majority of antidepressant side effects typically go away completely between 3-5 weeks, although this does not always take place. Practical techniques might reduce some of the negative effects in the meantime. Since TCAs are often sedatives, taking the prescription as directed before to sleep frequently reduces adverse effects throughout the day, particularly drowsiness. If a drug is recommended in split dosages, be sure to take the bigger dosage just before bed usually helps.
- Other typical adverse effects include forgetfulness, a “slowed down” or “spacey” mood, and feeling spacey and consist of signs and symptoms known as anticholinergic side effects, including as dry lips and skin, impaired vision, constipation, and trouble peeing. People usually become used to these side effects, but if severe anti-cholinergic effects are not constantly watched, they might cause disorientation and delirium, a mental illness.
- In some cases, the doctor may recommend a different drug to offset the anticholinergic effects of the antidepressant. For instance, a doctor could recommend a 1% pilocarpine eyedrop to address visual impairment and bethanechol, a cholinergic medication used to treat urinary tract issues (e.g., Urecholine). An over-the-counter stool softener like (docusate) is often beneficial for constipation.
- TCAs may cause dizziness in certain people. The medications’ ability to momentarily lower blood pressure may be the cause of dizziness since they prevent the body from responding appropriately when a person shifts from a laying down to a sitting or from a sitting to a standing posture. This response is referred to as orthostatic hypotension in medical terminology. Orthostatic hypotension caused by these antidepressants may be more common in elderly people and those on blood pressure drugs.
Another prevalent issue is weight gain, especially while using amitriptyline, (nortriptyline), and (doxepin). Most people who use TCAs gain several pounds.
if the patient’s condition does not improve, the doctor could consider switching the patient to a more recent class of weight-neutral antidepressants, including selective serotonin reuptake inhibitors (SSRIs).
TCAs may also result in decreased sexual desire in both men and women, as well as sexual issues such as impotence and difficulty ejaculating in males. Should this pose an issue, the doctor could replace the patient’s and switch to a different antidepressant that doesn’t affect sexual function, such bupropion.
Adverse Events and Safety Measures
As mentioned before, elderly people and those on blood pressure drugs may be very prone to the TCAs’ orthostatic hypotension. When abruptly standing up, patients on these antidepressants should use caution. Patients should slowly get up to a sitting posture if they are laying down prior to standing in order to prevent a sharp spike in blood pressure. If they feel lightheaded or dizzy, they should sit down and let their blood pressure a minute or two to normalize before getting up.
Tricyclic Antidepressants (TCAs) may also exacerbate narrow-angle glaucoma, a potentially dangerous eye ailment. Those who suffer this illness should let their psychiatrist know.
TCA usage has to be strictly watched in individuals with a history of seizure disease, since these antidepressants have the potential to reduce the threshold for seizures and induce them to occur. They could also slow down cardiac conduction, which might lead to an arrhythmia, a disruption in heart rhythm. This adverse reaction is more prevalent in older adults and those with a past medical history of cardiac arrhythmias. For these people, an ECG is advised before starting antidepressant medication and then again at regular intervals (at least once a year).
Overdosing
When taken in excess, TCAs may be very deadly, especially in young children. Overdoses often end in death, particularly when TCAs are used in conjunction with alcohol or other substances. Heart rhythm disturbance is often the primary factor in fatal TCA overdose deaths.
Treating any suspected overdose as an emergency is imperative. The individual has to be brought to the emergency space for care and observation. It is advisable to include both the prescription bottle of medicine and any other medication suspected in the overdose, since the information on the label may be useful in helping the treating physician figure out how many tablets the patient has taken.
Precautions Points to Remember
Major depressive disorder may often be effectively treated with medication, psychotherapy, or both. For the treatment of moderate to severe depression, the combination of psychotherapy and antidepressants is particularly successful. Medication enhances mood, energy, sleep, and appetite, while therapy helps people develop coping mechanisms, addresses any potential underlying problems and enhances behavior and mental habits.
60% to 70% of those who take antidepressants on their own report feeling better overall. The majority of people do not see noticeable advantages from their antidepressants until after 3–4 weeks, and it may sometimes take up to 8 weeks for the medicine to have its full effects. A small percentage of people may notice some improvement before the end of the first week. Therefore, it is crucial that patients take their antidepressant for the whole recommended amount of time and that they do not give up and stop taking it too soon if they do not start feeling better right away.
Although the precise processes by which antidepressants function are not entirely understood by researchers, it seems that they operate by interrupting a series of events that lead to irregularities in the brain’s processing of emotions or stress, which in turn causes the symptoms associated with depression. Given that TCAs all have comparable mechanisms of action, would it make sense for a doctor to prescribe a different TCA to a patient who is not responding to a tricyclic? In fact, individuals who don’t completely react to one antidepressant often do so to another in the identical class. Maybe not a good enough explanation for the conundrum. One individual may respond differently to an agent’s molecular structure than another.
To identify the ideal antidepressant, sometimes trial and error is necessary, or a mix of antidepressants, in order to effectively treat the patient.
Antidepressants have been shown in short-term trials to raise the likelihood of suicidal thoughts and actions in kids and teenagers suffering from severe depressive illness and other mental health issues. When beginning antidepressant treatment in children and adolescents, the FDA mandates that the prescriber disclose this risk to the patient.
- According to FDA research, there is an age-related risk of suicide thoughts and actions while using antidepressants. This phenomenon is more likely to manifest early in the course of and is more common in the younger population. Antidepressant use did not seem to be associated with a higher incidence of suicidality in people over the age of 24, as compared to placebo use. The results demonstrated that antidepressants have a “Protective effect” against acts and ideas of suicide. According to other research, there is a decrease in suicide rates in communities where a higher proportion of the population uses antidepressants.
- Suicide risk is a part of depression and may not go away until the patient responds to therapy. Keep a close eye out for behavioral changes, suicidal thoughts, and symptoms of deterioration in children and adolescents using antidepressants, particularly in the early stages of treatment and when doses are changed. Similarly, particularly in the first few months of treatment, people with depressive disorders who are taking antidepressants should be continuously monitored for any evidence of clinical deterioration and suicidal thoughts and acts.
- Warning: If you’re having suicidal thoughts, don’t hesitate to tell your doctor or a family member. Notify your family doctor or psychiatrist if you feel like you can’t control your suicide thoughts or desires, or if your depression symptoms become worse.
