Which Antidepressants Treat Comorbid Anxiety and Depression?
Is sertraline the best anxiolytic of the antidepressants? What other agents are available for concomitant anxiety and depression?
About 25% of individuals in the United States report experiencing an anxiety disorder at least once in a lifetime. Anxiety disorders may be diagnosed alone or with other psychiatric conditions. More than half of patients with depression have also been diagnosed with an anxiety disorder. An anxiety disorder may be a risk factor for a major depressive disorder, and the converse may be true as well. Consequently, anxiety should be identified and treated early to potentially prevent depression, as depression can worsen the clinical outcomes of various anxiety disorders.
Anxiety may be a symptom, a disease, or a comorbidity. The diagnosis will help determine the treatment modality. Some of the most common anxiety disorders include the following:
For patients with coexisting anxiety disorder and depression, psychotherapy, cognitive behavioral therapy, support groups, and other nonpharmacologic treatment modalities are effective and important for ensuring successful patient outcomes. Both acute and chronic management need to be considered. Depression should be treated first because addressing the psychological symptoms will often reduce the anxiety. Moreover, many of the agents used to treat depression also have anxiolytic effects.
Antidepressants such as selective serotonin reuptake inhibitors (SSRIs) (eg, sertraline, paroxetine, fluoxetine, escitalopram), serotonin-norepinephrine reuptake inhibitors (eg, venlafaxine), bupropion, and mirtazapine are often first-line agents because they also treat psychological symptoms of anxiety (eg, apprehension and worry). Tricyclic antidepressants (TCAs) (eg, amitriptyline, imipramine) are considered second-line treatments, given the concerns of safety and tolerability and potential exacerbations in suicidal patients.
When comparing overall efficacy between first-line agents for comorbid anxiety and depression, a few studies have demonstrated that venlafaxine is more effective than fluoxetine. However, these results must be viewed with caution because the studies varied considerably in terms of patient selection, assessment of anxiety, and primary outcome measures.
A systematic review of 28 randomized trials comparing specific antidepressant medications found no significant difference in symptom reduction in patients experiencing both depression and anxiety who received SSRIs compared with patients receiving other antidepressants. Additional head-to-head comparison studies are needed to fully evaluate differences in efficacy among the various agents.
When considering individual anxiety disorders, more evidence may support one class of antidepressant over another. Efficacy for treating GAD rests primarily with SSRIs. Mirtazapine and venlafaxine have demonstrated consistent benefit across the spectrum of anxiety disorders, as have the less tolerable TCAs. With respect to obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, and social phobia, SSRIs are the preferred agents, as TCAs have failed to show efficacy. A review of studies evaluating the use of SSRIs for the treatment of social anxiety disorder found that SSRIs are effective in reducing total levels of social anxiety and improving the overall clinical condition. Importantly, clinicians may find that patients have activation adverse events when beginning a serotonergic agent. This can result in a transient increase in anxiety requiring dose reduction, more gradual tapering, or change of antidepressant class.
Buspirone is a nonsedating nonbenzodiazepine with anxiolytic effects via serotonin and dopamine receptors. Buspirone is effective in treating GAD "positive" symptoms of worry, tension, irritability, and apprehension. It is less effective, however, for treatment of physical symptoms, such as changes in heart rate. Patients should take buspirone for a minimum of 3-6 weeks to evaluate its efficacy. Buspirone may be advantageous in patients with a history of substance abuse because it is not associated with dependence. Moreover, buspirone is associated with less to no tachyphylaxis.
Patients should receive follow-up care and monitoring to assess response and emerging side effects and to ensure adherence. When these agents are used only for depression, a 4- to 6-week response is expected. However, concomitant anxiety requires that the agents be tried at higher doses for a longer period of time (eg, 6-10 weeks). If a patient fails to respond to a first-line agent after an adequate trial, the class of antidepressant may be switched. If response is still poor, augmentation with another agent may be required. Augmenting agents include another antidepressant (eg, TCA, bupropion, or trazodone), thyroid hormone (synthetic T3), lithium, antiepileptic medications, and atypical antipsychotic drugs.
A Cochrane systematic review evaluated 10 randomized controlled trials comparing the efficacy of using antidepressants alone vs a combination of antidepressants and benzodiazepines for patients with depression and comorbid anxiety. Combining a benzodiazepine with an antidepressant was more effective for reducing depressive symptoms. That said, the potential benefits of adding a benzodiazepine to an antidepressant must be weighed against possible harms, such as dependence and accident proneness in the elderly.
High-potency benzodiazepines are preferred because they are associated with less rebound anxiety, fewer peak effects (eg, sedation), less psychomotor slowing, and less antegrade amnesia. However, benzodiazepines should be restricted to use as "rescue" medication and administered only for short durations of time because of the potential for tachyphylaxis. For the acute management of an anxiety attack, benzodiazepines are effective for controlling immediate physical symptoms. The fast onset of benzodiazepines will provide a temporary anxiolytic effect while antidepressants used to treat the underlying worrying and apprehension are initiated.
In conclusion, antidepressants and benzodiazepines are the most commonly employed agents used to treat anxiety disorders. However, they do not address the root cause of the anxiety. As such, cognitive behavioral therapy is another critical piece of the therapeutic puzzle addressing depression and comorbid anxiety. Family and individual counseling and group support may also be indicated, especially in teens where suicidality during use of an SSRI or a serotonin-norepinephrine reuptake inhibitor has been documented. Overall, the patient as a whole must be considered and treated, as reliance on medications alone may not resolve the underlying patient issues.
The author would like to acknowledge the contributions and assistive research of Jessica Stovel, clinical pharmacist, London Health Sciences Centre, Victoria Hospital.
Is sertraline the best anxiolytic of the antidepressants? What other agents are available for concomitant anxiety and depression?
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Response from Joel Lamoure, RPh, BSP Assistant Professor and Assistant CME Director, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada; Mental Health Pharmacist, London Health Sciences Centre, South Street Hospital, London, Ontario, Canada |
About 25% of individuals in the United States report experiencing an anxiety disorder at least once in a lifetime. Anxiety disorders may be diagnosed alone or with other psychiatric conditions. More than half of patients with depression have also been diagnosed with an anxiety disorder. An anxiety disorder may be a risk factor for a major depressive disorder, and the converse may be true as well. Consequently, anxiety should be identified and treated early to potentially prevent depression, as depression can worsen the clinical outcomes of various anxiety disorders.
Anxiety may be a symptom, a disease, or a comorbidity. The diagnosis will help determine the treatment modality. Some of the most common anxiety disorders include the following:
Generalized anxiety disorder (GAD)
Obsessive-compulsive disorder
Panic disorder
Social phobia/social anxiety disorder
Post-traumatic stress disorder
For patients with coexisting anxiety disorder and depression, psychotherapy, cognitive behavioral therapy, support groups, and other nonpharmacologic treatment modalities are effective and important for ensuring successful patient outcomes. Both acute and chronic management need to be considered. Depression should be treated first because addressing the psychological symptoms will often reduce the anxiety. Moreover, many of the agents used to treat depression also have anxiolytic effects.
Antidepressants such as selective serotonin reuptake inhibitors (SSRIs) (eg, sertraline, paroxetine, fluoxetine, escitalopram), serotonin-norepinephrine reuptake inhibitors (eg, venlafaxine), bupropion, and mirtazapine are often first-line agents because they also treat psychological symptoms of anxiety (eg, apprehension and worry). Tricyclic antidepressants (TCAs) (eg, amitriptyline, imipramine) are considered second-line treatments, given the concerns of safety and tolerability and potential exacerbations in suicidal patients.
When comparing overall efficacy between first-line agents for comorbid anxiety and depression, a few studies have demonstrated that venlafaxine is more effective than fluoxetine. However, these results must be viewed with caution because the studies varied considerably in terms of patient selection, assessment of anxiety, and primary outcome measures.
A systematic review of 28 randomized trials comparing specific antidepressant medications found no significant difference in symptom reduction in patients experiencing both depression and anxiety who received SSRIs compared with patients receiving other antidepressants. Additional head-to-head comparison studies are needed to fully evaluate differences in efficacy among the various agents.
When considering individual anxiety disorders, more evidence may support one class of antidepressant over another. Efficacy for treating GAD rests primarily with SSRIs. Mirtazapine and venlafaxine have demonstrated consistent benefit across the spectrum of anxiety disorders, as have the less tolerable TCAs. With respect to obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, and social phobia, SSRIs are the preferred agents, as TCAs have failed to show efficacy. A review of studies evaluating the use of SSRIs for the treatment of social anxiety disorder found that SSRIs are effective in reducing total levels of social anxiety and improving the overall clinical condition. Importantly, clinicians may find that patients have activation adverse events when beginning a serotonergic agent. This can result in a transient increase in anxiety requiring dose reduction, more gradual tapering, or change of antidepressant class.
Buspirone is a nonsedating nonbenzodiazepine with anxiolytic effects via serotonin and dopamine receptors. Buspirone is effective in treating GAD "positive" symptoms of worry, tension, irritability, and apprehension. It is less effective, however, for treatment of physical symptoms, such as changes in heart rate. Patients should take buspirone for a minimum of 3-6 weeks to evaluate its efficacy. Buspirone may be advantageous in patients with a history of substance abuse because it is not associated with dependence. Moreover, buspirone is associated with less to no tachyphylaxis.
Patients should receive follow-up care and monitoring to assess response and emerging side effects and to ensure adherence. When these agents are used only for depression, a 4- to 6-week response is expected. However, concomitant anxiety requires that the agents be tried at higher doses for a longer period of time (eg, 6-10 weeks). If a patient fails to respond to a first-line agent after an adequate trial, the class of antidepressant may be switched. If response is still poor, augmentation with another agent may be required. Augmenting agents include another antidepressant (eg, TCA, bupropion, or trazodone), thyroid hormone (synthetic T3), lithium, antiepileptic medications, and atypical antipsychotic drugs.
A Cochrane systematic review evaluated 10 randomized controlled trials comparing the efficacy of using antidepressants alone vs a combination of antidepressants and benzodiazepines for patients with depression and comorbid anxiety. Combining a benzodiazepine with an antidepressant was more effective for reducing depressive symptoms. That said, the potential benefits of adding a benzodiazepine to an antidepressant must be weighed against possible harms, such as dependence and accident proneness in the elderly.
High-potency benzodiazepines are preferred because they are associated with less rebound anxiety, fewer peak effects (eg, sedation), less psychomotor slowing, and less antegrade amnesia. However, benzodiazepines should be restricted to use as "rescue" medication and administered only for short durations of time because of the potential for tachyphylaxis. For the acute management of an anxiety attack, benzodiazepines are effective for controlling immediate physical symptoms. The fast onset of benzodiazepines will provide a temporary anxiolytic effect while antidepressants used to treat the underlying worrying and apprehension are initiated.
In conclusion, antidepressants and benzodiazepines are the most commonly employed agents used to treat anxiety disorders. However, they do not address the root cause of the anxiety. As such, cognitive behavioral therapy is another critical piece of the therapeutic puzzle addressing depression and comorbid anxiety. Family and individual counseling and group support may also be indicated, especially in teens where suicidality during use of an SSRI or a serotonin-norepinephrine reuptake inhibitor has been documented. Overall, the patient as a whole must be considered and treated, as reliance on medications alone may not resolve the underlying patient issues.
The author would like to acknowledge the contributions and assistive research of Jessica Stovel, clinical pharmacist, London Health Sciences Centre, Victoria Hospital.