Side Effects from Medical Conditions and Antidepressant Use

Depression is often found in comorbidity with different medical conditions, increasing the chance that antidepressants may contribute to adverse effects. Some are rare and carry some potential risk, but most effects are mild, temporary, and often diminish on their own. When being treated for multiple conditions, consult your healthcare professional if you notice unusual symptoms and take all medications as prescribed unless advised otherwise.

Read on to learn about uncommon effects that may occur with medical conditions and antidepressant treatments.

SSRI cardiac side effects

Cardiovascular Disease

Cardiovascular disease and depressive disorders are linked and often occur together. Awareness of uncommon adverse effects can help individuals lower their risk of SSRI cardiac side effects while effectively treating their depressive disorder.

  • Research has revealed that SSRIs and hemorrhagic strokes may be connected, particularly recurrent strokes after the initial event. These two conditions have been shown to occur together infrequently, and no causality has been established between them. Individuals with hypertension or other risk factors for intracerebral hemorrhaging may instead consider tricyclics, a class of antidepressants not known for increased risk of bleeding.
  • Several antidepressants have been linked with prolonged QT interval, a rare heart rhythm disorder where the interval between heart muscle contraction and relaxation is longer than usual. The risk of developing prolonged QT interval is higher with amitriptyline, imipramine, maprotiline, citalopram, and escitalopram. An uncommon but potentially serious arrhythmia called Torsade de Pointes (TdP) may arise if a prolonged interval has developed, though it is an unlikely occurrence. Fluoxetine, fluvoxamine, paroxetine, and sertraline have a low association with prolonged QT interval and may be considered as a lower-risk option.
  • Case reports suggest that tricyclics may be linked with a risk of cardiomyopathy, a progressive heart muscle disease impairing its ability to pump blood efficiently. The incidence of this condition in connection with tricyclics appears to be low, and risk may be avoided by choosing SSRI or SNRI antidepressants.
  • SSRIs have been considered a low-risk option regarding cardiac side effects. Still, increasing evidence has emerged linking their use to an elevated risk of atherogenesis, the buildup of plaque in the arteries that can lead to coronary artery disease often found in elderly adults. For older individuals needing depression treatment, this increased risk of cardiovascular disease may be mitigated by choosing psychological treatment when possible and monitoring heart functioning during SSRI treatment as a precaution.

Gastrointestinal Bleeding

Gastrointestinal bleeding is an uncommon but established adverse effect of SSRI use, with up to a 41% greater chance than individuals not taking SSRIs. The greatest risk presents for individuals also taking non-steroidal anti-inflammatory drugs (NSAIDs), such as high-dose aspirin or ibuprofen, or antiplatelet medications. It is thought that the serotonin reuptake inhibition induced by antidepressants also inhibits platelet activity. This effect impairing clotting and the body’s ability to slow the rate of blood flow, two essential healing functions that prevent excess blood loss.

To reduce the chance of bleeding, individuals may consider limiting NSAID use, understand the signs of potential gastrointestinal bleeding, and consider using acid-suppressant. Individuals should avoid stopping medication based on bleeding risk alone should be avoided if the benefits of treatment are meaningful.


Research shows an elevated risk of seizures for all classes of antidepressants, though the chances of one occurring are small. Involuntary, sudden movements called myoclonus are potentially linked with increased serotonin activity, the same neurotransmitter channel impacted by antidepressants.

Though the absolute risk of seizures is low, individuals concerned about this risk may consider using escitalopram, sertraline, and mirtazapine. None of these medications are associated with increased seizure activity.

Inadequate Drug Metabolism

Variants of the gene CYP2C19 can lead to a rare condition resulting in inadequate drug metabolism. While this effect is not harmful, it may contribute to an ineffective antidepressant response to SSRIs escitalopram and citalopram. Lack of treatment response prolongs the wait for effective symptom relief and may indicate treatment-resistant depression, implicated by two inadequate responses to antidepressant medication.

Identifying this gene variant can help individuals turn toward other treatment options that may be more effective for treatment-resistant depression, such as a different antidepressant family, various types of psychotherapy, or Deep transcranial magnetic stimulation (Deep TMS™). Deep TMS is an FDA-cleared, noninvasive treatment utilizing electromagnetic pulses to regulate neural activity in the brain, showing efficacy when response to other treatments has been inadequate or incomplete.

Bipolar Depression Disorder

First-generation antidepressants such as tricyclics have been shown at times to trigger manic episodes, a period of abnormally elevated mood, high energy, and decreased need for sleep. Individuals with bipolar disorder should consider second-generation or newer antidepressants, including SSRIs, SNRIs, and atypical antidepressants. Mood stabilizers are medications used to help regulate manic and depressive mood shifts. Including them in an individual’s treatment medication regimen may further help them avoid the appearance of a manic episode.

The underlying disorder also relates to an individual’s sensitivity to manic episodes. Individuals with major depression are far less likely to experience manic symptoms than those with bipolar disorder. Some presenting with bipolar disorder may, in fact, have major depression with false hypomanic episodes, periods of manic symptoms that are less intense. These uncertainties can be challenging when determining an individual’s risk for emergent manic episodes.

SSRI treatment efficacy does not increase exponentially as one’s dosage is increased—a key point for those trying to minimize their risk of inducing manic symptoms. Rather, SSRIs’ efficacy and dosage increase together in a linear fashion up to a point, after which their efficacy drops as the dosage continues to increase. Better tolerance is also more likely at lower doses, thereby providing a range more likely to provide therapeutic benefit with a reduced risk of side effects and periods of mania.

Choosing Antidepressants+

Choosing Antidepressants: Balancing Therapeutic Impact with Side Effects

Antidepressant treatments may be a beneficial part of treatment plans addressing disorders such as depression and OCD. While some side effects may be mildly uncomfortable for short periods, others can be more unexpected and concerning at times. By consulting with their healthcare provider, individuals choose an antidepressant treatment with a better understanding of how medical conditions may impact their decision.