Bipolar Disorder Treatment with SSRIs and SNRIs Antidepressants

Both bipolar I and bipolar II types commonly present with depressive episodes, often in combination with episodes of mania. To treat these depressive episodes and the related symptoms that may occur during the acute phase or maintenance phase, such as anxiety or difficulty sleeping, clinicians may prescribe an SSRI or SNRI.^[1] However, prescribing these antidepressants requires careful consideration, as there is conflicting evidence supporting their efficacy, and some clinicians have concerns about the affective switching and mood destabilization they could cause.^[2]

This article explores the controversy and uncertainty surrounding the prescription of antidepressants for bipolar disorder, delving into both the potential benefits and adverse effects.

What Are SSRIs and SNRIs?

Both of these medications are known as reuptake inhibitors and are prescribed to treat numerous mental health conditions, including depression and anxiety.

Selective Serotonin Reuptake Inhibitors (SSRIs) block the reuptake of serotonin, a neurotransmitter that regulates sleep, memory, and mood. By blocking this neurotransmitter from being reabsorbed, the drug can actually increase the concentration and availability of serotonin in your body.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) block the reuptake of both serotonin and norepinephrine, another neurotransmitter that’s involved with alertness, focus, and taking action. SNRIs therefore increase the concentration and availability of both neurotransmitters it acts on.

SSRIs and SNRIs have notable benefits and side effects – these should be discussed with a qualified professional before they are prescribed. Though these drugs are primarily used for treating unipolar depression (major depressive disorder), clinicians may recommend either SNRI or SSRI drugs for bipolar disorder too.

The Controversy of Antidepressants in Bipolar Disorder Treatment

To understand the controversy between antidepressants and bipolar disorder, let’s first understand some defining episodes of bipolar disorder.

• Depressive episodes: low mood and total loss of enjoyment that persists for at least 2 weeks but may continue for months at a time. Symptoms may include insomnia, lack of concentration, extreme sadness, and feelings of worthlessness.
• Manic episodes: abnormally energetic and elevated mood, typically goal-oriented, that persists for at least 7 consecutive days. Symptoms may include delusions, hallucinations, illogical reasoning, and high-risk decision-making.
• Rapid cycling: distinct episodes of mania or depression that cycle at least 4 times within 1 year.^[3]

As aforementioned, antidepressants including SSRIs and SNRIs are commonly prescribed for depression and may be used to treat the symptoms common to a depressive episode. However, bipolar disorder is a complex condition that involves more than just depression. Thus, prescribing antidepressants may not be an effective treatment overall or in the long term.

This is where much of the clinical uncertainty regarding the use of antidepressants for patients with bipolar disorder lies. Controversy regarding the use of antidepressants for depressive episodes of bipolar disorder has been prevalent since the 1980s.

Numerous studies and reviews have been conducted over the decades, yet evidence of their effectiveness remains elusive. In fact, some studies have suggested that antidepressants may possibly increase the risk of triggering manic episodes and rapid cycling.^[4]

Due to this controversy and lack of evidence, current medical guidelines do not recommend using antidepressants as a first-line treatment for any form of bipolar disorder.

Type I vs Type II

When exploring the controversy of antidepressants for bipolar disorder, it is worth noting the differences between type I bipolar disorder and type II bipolar disorder.

For example, in a 2024 issue of the American Journal of Psychiatry, a study looked at 979 bipolar individuals who were discharged after admittance for bipolar depression. It concluded that there were “no significant associations between allocation to antidepressant treatment and recurrence of mania or hypomania.”

Notably, the authors of the article note that bipolar II is dominated more by depression than bipolar I. This means that it’s likely that the sample of patients they studied consisted of a greater number of bipolar II patients than bipolar I patients.

This is noteworthy as evidence suggests that switching to antidepressant treatment is much less likely to occur in bipolar II than in bipolar I. This does impact the overall outcome of the research and should be kept in mind when using such data to inform medication recommendations.

Ultimately, you can find reputable studies both confirming and denying the occurrence of manic episodes and rapid cycling triggered by antidepressant treatments. More research is needed to conclude definitively one way or the other.

SSRIs in Bipolar Disorder Treatment

For depressive disorders, SSRIs are often prescribed before SNRIs as they have fewer side effects. They may also be prescribed to help individuals with bipolar disorder during depressive episodes to reduce feelings of sadness and promote a more balanced, positive mood.

SSRIs that may be prescribed for bipolar disorder include:

• Fluoxetine (Prozac)
• Sertraline (Zoloft)
• Citalopram (Celexa)

Common side effects of SSRIs include:

• Heart palpitations
• Reduced appetite
• Nausea
• Insomnia
• Anxiety
• Sexual dysfunction
• Hyperhidrosis (excessive sweating)^[5]

Importantly, the National Institute for Health and Care Excellence (NICE) states that even the best SSRI for bipolar shouldn’t be prescribed for or during a manic phase of bipolar disorder.

SNRIs for Bipolar Depression

SNRIs impact both serotonin and norepinephrine. They are commonly prescribed for depression and anxiety disorders but can also be prescribed for chronic nerve pain. A clinician may prescribe an SNRI (as an alternative to an SSRI) alongside a mood stabilizer to treat bipolar depression, although this class of drugs is mainly reserved for unipolar depression.^[6]

SNRIs that may be prescribed for bipolar disorder include:

• Desvenlafaxine (Pristiq)
• Duloxetine (Cymbalta)
• Venlafaxine (Effexor)

Common side effects of SNRIs include:

• Insomnia
• Nausea
• Weight gain
• Sexual dysfunction
• Agitation^[7]

One rare adverse effect of the antidepressants listed above is suicidal ideation. This is yet another controversy in the mental health field. Since 2004, the FDA has decreed that a warning regarding the risk of suicidality be printed on the medication box. However, a decrease in how often these drugs are prescribed and a recent increase in the number of suicidal events among people with severe depression has made some experts question the efficacy of this warning.^[8]

Whether you have bipolar disorder, depression, or any mental health condition or symptom, it is important that you talk to a qualified medical professional for any advice regarding antidepressants.

Monitoring and Managing Side Effects of Antidepressants

The adverse effects listed above, including suicidal ideation, are common to antidepressants regardless of who they are prescribed to. However, there are side effects of antidepressants that could be unique to individuals with bipolar disorder.

Prescribing antidepressants for bipolar disorder may “be associated with long-term worsening of the course of illness (mainly rapid-cycling) in about one-third of bipolar subjects” according to some studies. It may also increase the risk of mania.^[9]

For this reason, it is essential that healthcare providers take a cautious approach to prescribing antidepressants and closely monitor patients to ensure the medication is discontinued if adverse effects are reported.

Special Considerations for Bipolar Patients

For bipolar patients suffering from depressive episodes, antidepressants could offer a welcome reprieve from their symptoms. However, as we’ve outlined, it’s important for clinicians to prescribe antidepressants cautiously due to the controversy surrounding their efficacy.

Current guidance, including guidance from the American Psychiatric Association (APA), recommends that antidepressants should only be used in combination with mood stabilizers or introduced after them at a later point in the treatment plan.^[9]

It may be advisable for clinicians to reserve antidepressants for severe cases of acute bipolar depression (rather than mild to moderate cases) and promptly discontinue their use after the depressive episode resolves.^[10]

Furthermore, clinicians can consider:

• Shorter treatment schedules.
• Lower doses compared to those recommended for unipolar depression.
• Carefully selecting the best antidepressant for bipolar patients based on guidance from the APA.

Alternative Treatments for Bipolar Depression

Patients with mild to moderate cases of bipolar depression may still suffer some intense symptoms during depressive episodes. If they are unwilling to take antidepressants—or their clinician determines that they are an unsuitable course of treatment—there may be alternative treatments available.

It’s not at all uncommon for patients to receive these alternative treatments. In fact, a study found that only 9% of patients were treated with antidepressant monotherapy, which means they were taking only one antidepressant medication. In contrast, 54% of patients were treated with mood stabilizers and 50% with antipsychotics.^[9]

Alternative treatments that may be discussed include:

• Quetiapine: this antipsychotic drug is most effective for treating mania but has also shown some efficacy for treating depression.
• Lithium: this mood stabilizer has been shown to reduce the risk of manic relapses by 38% and depressive relapses by 28%. It has also been shown to have neuroprotective effects, regulate the circadian rhythm, and can be used as an anti-suicidal treatment.^[11]
• Psychosocial treatments: a combination of pharmacotherapy and targeted psychotherapy can help to prevent relapses and worsening symptomatic states. Learning how to manage stress and maintain a healthy lifestyle can aid long-term management of depressive episodes.^[12]

Combining Antidepressants with Mood Stabilizers

The current recommended course of treatment is mood stabilizers as monotherapy or a combination of mood stabilizers with antidepressants for bipolar disorder. This common practice relies on the evidence-based benefits of mood stabilizers for patients with bipolar disorder and supplements with antidepressants for managing the symptoms of depressive episodes.

Dr. Ghaemi, Director of the Bipolar Disorders Program at Emory University School of Medicine, has stated that:

“Clinicians and perhaps patients seem to be constantly searching for drugs other than mood stabilizers in the treatment of bipolar disorder, yet the evidence is hard to ignore that this illness does not improve without mood stabilizers at the core of any treatment regimen.”^[9]

Conclusion

It is clear that despite the controversy surrounding the use of SSRI and SNRI antidepressants for the treatment of bipolar disorder, patients have a range of treatment options available to them. With mood stabilizers at the core of many treatment programs, the short-term and carefully monitored use of antidepressants could help manage depressive episodes, though more research is needed to truly weigh the benefits and risks to patients.