What antidepressant works well with lorazepam? Combining short-term relief with long-term therapy

October 10, 2025 •

4 min read

Research indicates that the combination of benzodiazepines like lorazepam and antidepressants is a frequent clinical strategy for patients with co-occurring anxiety and depressive disorders. Therefore, the question of what antidepressant works well with lorazepam is less about finding a single 'best' combination and more about understanding the different classes of medication that can be safely and effectively combined for a short-term bridging strategy.

Quick Summary

Healthcare providers often combine lorazepam with long-acting antidepressants, like SSRIs or SNRIs, to provide immediate anxiety relief while awaiting the antidepressant's full therapeutic effect. This approach requires careful monitoring due to additive sedation risks and the potential for dependence with extended lorazepam use.

Key Points

SSRI/SNRI Combination: SSRIs (e.g., escitalopram, sertraline) and SNRIs (e.g., duloxetine) are commonly paired with lorazepam as a short-term bridging strategy for anxiety.
Bridge Medication Strategy: Lorazepam provides immediate relief for acute anxiety symptoms while the long-term antidepressant medication begins to take effect, which can take several weeks.
Additive CNS Depression: The main safety concern when combining lorazepam with most antidepressants is the increased risk of central nervous system (CNS) depression, which can cause excessive sedation, dizziness, and confusion.
Short-Term Use Only: Due to the high potential for physical dependence, lorazepam is intended for short-term use, and patients are typically tapered off the medication once the antidepressant is effective.
Medical Supervision is Crucial: Combining these medications should only be done under the strict supervision of a healthcare provider, who can monitor for side effects and manage the tapering process safely.
Individualized Treatment: The best medication combination is highly dependent on individual factors, including the specific condition, patient health, and response to treatment.

Combining different classes of psychotropic medications is a common practice in clinical settings, particularly when treating complex mental health conditions such as anxiety and depression. A typical scenario involves using a fast-acting benzodiazepine like lorazepam (Ativan) for short-term symptom relief, while a longer-acting antidepressant is started to manage the condition over the long term. Lorazepam, which works by enhancing the effects of gamma-aminobutyric acid (GABA), offers rapid but temporary relief from anxiety, insomnia, and panic attacks. Antidepressants, which include selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are considered first-line, long-term therapies for anxiety and depression.

The Role of Lorazepam in Combination Therapy

When initiating treatment with an antidepressant, it can take several weeks for the medication to reach its full therapeutic effect. During this initial period, some patients may experience heightened anxiety or other unpleasant side effects, which can lead to early discontinuation of treatment. Lorazepam serves as a valuable "bridge" medication in this context. By providing rapid relief from severe anxiety symptoms, it helps patients tolerate the initial adjustment phase of the antidepressant, improving overall treatment adherence and outcome.

However, healthcare providers must be mindful of the risks associated with long-term benzodiazepine use, most notably the potential for physical dependence and withdrawal symptoms upon cessation. As a result, the combination of lorazepam and an antidepressant is typically a short-term strategy, with a planned tapering of the lorazepam once the antidepressant becomes effective.

Antidepressant Classes Often Used with Lorazepam

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are a common choice for combination therapy with lorazepam. They work by increasing serotonin levels in the brain, improving mood and reducing anxiety over time. Examples include sertraline (Zoloft), escitalopram (Lexapro), and paroxetine (Paxil).

Benefits: SSRIs are generally well-tolerated and effective for both anxiety and depression. They are non-addictive, making them suitable for long-term management.
Considerations with Lorazepam: Combining an SSRI like sertraline with lorazepam can increase side effects such as drowsiness and dizziness due to the additive central nervous system (CNS) depressant effects. Patients should be monitored closely, especially during dosage adjustments.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs, such as duloxetine (Cymbalta), increase both serotonin and norepinephrine levels. They are also effective for anxiety and depression and are often used as first-line treatment.

Benefits: SNRIs can be beneficial for patients experiencing fatigue, as norepinephrine can have a stimulating effect. They are also non-addictive.
Considerations with Lorazepam: Similar to SSRIs, combining SNRIs with lorazepam can enhance CNS depression, potentially increasing drowsiness, dizziness, and coordination issues.

Other Antidepressants

Other classes of antidepressants may be used, though some carry different or more significant risks in combination with benzodiazepines.

Tricyclic Antidepressants (TCAs): Older antidepressants like amitriptyline can be used, but caution is warranted due to their potential for additive CNS depression when combined with lorazepam.
Trazodone: An antidepressant often used off-label for insomnia, trazodone can be combined with lorazepam under strict medical supervision. However, the combination can cause extreme sedation and carries a risk of respiratory problems.

Comparison of Antidepressant Classes with Lorazepam


Antidepressant Class	Common Examples	How it Works	Considerations with Lorazepam
SSRIs	Escitalopram, Sertraline, Paroxetine	Increases serotonin in the brain	Generally well-tolerated, but can increase sedation, drowsiness, and dizziness
SNRIs	Duloxetine	Increases serotonin and norepinephrine	Can enhance sedative effects, leading to increased drowsiness and impaired coordination
TCAs	Amitriptyline	Increases serotonin and norepinephrine; blocks acetylcholine and histamine	Significant potential for additive CNS depression; careful monitoring is essential
Other	Trazodone	Blocks serotonin receptors and inhibits reuptake	Risk of extreme sedation and respiratory depression; requires careful medical supervision

Safety Considerations and Management

Regardless of what antidepressant works well with lorazepam for an individual, careful management is essential. Healthcare providers must monitor for the following safety concerns:

Increased Sedation: The most significant risk is the additive effect of two CNS depressants. This can lead to excessive drowsiness, dizziness, and impaired motor skills, increasing the risk of falls and accidents.
Dependence and Withdrawal: Lorazepam has a high potential for physical dependence, and abrupt discontinuation can lead to severe withdrawal symptoms. A gradual tapering plan is necessary when discontinuing the medication.
Comorbid Conditions: The presence of other health issues, such as sleep apnea or liver problems, may increase the risks of combining medications.
Alcohol and Other Substances: Combining lorazepam with alcohol or other substances that depress the CNS is extremely dangerous and can be life-threatening.
Serotonin Syndrome: While rare, monitoring for serotonin syndrome is important, especially during the initial phase or dosage adjustments.

The Patient's Role in Safe Combination Therapy

Successful management of combination therapy depends on clear communication and active patient participation. Patients should fully disclose all medications, including over-the-counter products, supplements, and alcohol or recreational substance use. Following the prescribed regimen precisely and never altering the dose without consulting a healthcare provider is critical. Understanding the short-term nature of the lorazepam and the long-term goal of the antidepressant therapy is key for optimal outcomes.

Conclusion

When determining what antidepressant works well with lorazepam, the focus is on a safe, temporary combination that leverages lorazepam's fast-acting anxiety relief while allowing the long-term antidepressant to take effect. SSRIs and SNRIs are most commonly used for this purpose, with careful monitoring for additive CNS depressant effects. Long-term use of lorazepam is discouraged due to dependence risks, emphasizing the importance of a planned taper. Ultimately, the most effective and safest approach is determined on a case-by-case basis under the close supervision of a healthcare provider.

For more information on the combined use of antidepressants and benzodiazepines, consult peer-reviewed research and meta-analyses.

Frequently Asked Questions

Yes, it is a common practice for doctors to prescribe lorazepam with an SSRI or SNRI simultaneously, especially at the start of antidepressant therapy. The lorazepam provides immediate relief from anxiety while the longer-acting antidepressant builds up in your system.

The most common side effect is increased central nervous system (CNS) depression, which can cause excessive drowsiness, dizziness, confusion, and impaired coordination. These effects can be more pronounced when starting treatment or with dosage changes.

No, long-term use of lorazepam is not generally recommended due to the high risk of physical dependence and addiction. The typical strategy is to use lorazepam for a short period, then gradually taper off as the antidepressant becomes effective.

Antidepressants typically take several weeks to produce a noticeable therapeutic effect. This is why a bridging medication like lorazepam can be helpful for initial symptom management.

Because of the risk of physical dependence, abruptly stopping lorazepam can lead to withdrawal symptoms, which can include anxiety, restlessness, and seizures. A gradual tapering schedule, supervised by a doctor, helps minimize these risks.

While many combinations are possible under medical guidance, certain medications require extra caution. For example, combining trazodone with lorazepam carries a risk of extreme sedation and breathing problems, and TCAs can also cause significant additive CNS depression.

If you experience excessive drowsiness, dizziness, or impaired coordination, you should avoid activities that require alertness, such as driving or operating machinery. Always discuss these side effects with your prescribing healthcare provider, who may adjust your dosage.

While the combination itself doesn't directly cause serotonin syndrome, monitoring is always recommended when adjusting antidepressant dosages, particularly within the first 24 to 48 hours of a change. Serotonin syndrome is a risk with SSRIs/SNRIs, and any changes in mental status should be reported to a doctor.