Anxiety Management

When deciding which medications for anxiety disorders to offer, take into account:

• Choice of agent will be based on the STEPS principle:
  • Safety (patient profile, side effect profile, toxicity, drug interactions and long-term safety data)
  • Tolerability (manageability of side-effects, patient adherence)
  • Efficacy (based on clinical data, real-world use)
  • Price (cost)
  • Simplicity (dosing schedule, route of administration, patient preference)

Benzodiazepines  

Benzodiazepines act through the enhancement of gamma-aminobutyric acid (GABA) which is a major inhibitory neurotransmitter in the brain which leads to reduced neural transmission throughout the central nervous system (CNS). They are recommended for short-term treatment with regular use. Physical dependence and tolerance may develop. They are used with caution in patients with a history of substance abuse or drug use.  

Generalized Anxiety Disorder  

Benzodiazepines are widely used in GAD. Diazepam or Clonazepam may be used due to their rapid response and long duration of action. Both short- and long-acting benzodiazepines have been proven to have a rapid onset of anxiolytic action. They effectively decrease somatic symptoms. They do not reduce depressive symptoms, and they have limited effect on reducing worry. Benzodiazepines are recommended to limit use for acute treatment. They may be used as an adjunct for long-term treatment if there is no occurrence of serious side effects, misuse or abuse. They should not be used beyond 2 to 4 weeks.  

Panic Disorder  

Benzodiazepines may be added to antidepressants for up to 4 weeks (short-term) for rapid response then tapered down and withdrawn by 4 weeks. They may be used as second-line or alternative agents. Alprazolam, Clonazepam, Lorazepam, and Diazepam have demonstrated efficacy. Studies have shown that the addition of Clonazepam to SSRI at the start of treatment can lead to rapid response. They reduce the frequency and intensity of panic attacks and reduce anticipatory anxiety. They may also lead to decreased avoidance of phobias. Benzodiazepines have a rapid onset of action in panic disorder. However, they are associated with less good-long term outcomes than antidepressants.  

Social Anxiety Disorder  

Benzodiazepines in SAD may be used with SSRI or serotonin and norepinephrine reuptake inhibitors; however, available literature is not available to support this. They are not recommended as monotherapy for patients with concomitant depression. They also have a rapid onset of action in SAD. Lastly, it must be noted that relapses occur upon withdrawal are common.

Azaspirodecanedione  

Buspirone  

Buspirone has dopaminergic, noradrenergic, and serotonin-modulating properties. Its anxiolytic effects seem to be due to its action on serotonin.  

Generalized Anxiety Disorder  

Buspirone may be used as a second-line agent in GAD. It may be considered as adjunctive treatment with CBT in patients with partial response to first-line agents. It is useful in patients with a history of substance abuse. It has been shown to be as effective as benzodiazepines. Compared to benzodiazepines, it is more effective in treating cognitive rather than somatic symptoms, it does not cause physical dependence or tolerance, it takes 2 to 3 weeks to see effect with an average of 4 weeks, and effects may be reduced in patients who have been recently taken benzodiazepines. They are not suitable for patients with comorbid depression.

Selective Serotonin Reuptake Inhibitors (SSRI)  

SSRIs are recommended first-line during drug treatment for anxiety disorders. All SSRIs are thought to be equally effective; however, they differ in their side profiles.  

Generalized Anxiety Disorder  

Not all SSRI have been studied or approved for use in GAD. Sertraline is considered as the first drug to use because it is the most cost-effective among the SSRI. Other SSRI recommended are Escitalopram and Paroxetine. SSRIs may be more effective than benzodiazepines. SSRI provides greater benefit than benzodiazepines for decreasing cognitive issues. They do not cause physical dependence or tolerance. It has a slower onset of action than benzodiazepines, and they are not suitable for patients with comorbid depression.  

Panic Disorder  

Not all SSRI have been approved for use in PD, but studies have shown all are helpful in PD. SSRIs that can be used in PD include Citalopram, Escitalopram, Fluoxetine, Paroxetine, and Sertraline. They are better tolerated and with better adverse effect profile compared to older antidepressants. They reduce the frequency and intensity of panic attacks and reduce anticipatory anxiety and depression.  

Social Anxiety Disorder  

Many studies of certain SSRI have shown efficacy. Citalopram, Escitalopram, Fluvoxamine, Paroxetine or Sertraline can be considered. In SAD, they are suitable for patients with comorbid depression.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)  

Venlafaxine  

Venlafaxine is considered as a first-line agent for GAD, PD, and SAD. It requires an initial electrocardiogram (ECG) and blood pressure (BP) reading prior to treatment.  

Generalized Anxiety Disorder  

Studies on Venlafaxine have shown therapeutic benefit in GAD in both long- and short-term use. Notably, improvement has been observed after 1 week of treatment. It has been found to be suitable for patients with comorbid depression. Venlafaxine in GAD has been reported to improve social functioning and to reduce ruminative worry.  

Panic Disorder  

Studies have shown that Venlafaxine reduces severity of symptoms in PD.  

Social Anxiety Disorder  

The efficacy of Venlafaxine in SAD is established in four 12-week randomized controlled trials (RCTs). It has been shown to significantly reduce the patient's SAD symptoms within 4 to 6 weeks.

Duloxetine  

Duloxetine is considered as the first-line agent in GAD.  

Tricyclic Antidepressants (TCAs)

Generalized Anxiety Disorder  

Imipramine is the only agent that has consistently shown benefit in GAD. It may be used as an alternative treatment for GAD. It has a slower onset of action than benzodiazepines but is shown to be as effective. It is noted to be more effective in treating psychic rather than somatic symptoms. It is also suitable for patients with comorbid depression. Lastly, the adverse effects are usually the limiting factor.  

Panic Disorder  

TCAs used in PD include Clomipramine and Imipramine. They may be used as an alternative treatment for PD. Imipramine is the most extensively studied TCA. They reduce the frequency and intensity of panic attacks, reduce anticipatory anxiety and associated depression. They may also lead to decreased avoidance of phobias. The adverse effects are the usual limiting factor for use.

Noradrenergic and Specific Serotonergic Antidepressant (NaSSA)  

Generalized Anxiety Disorder  

Mirtazapine may be considered for GAD for its anxiolytic effects for refractory anxiety with insomnia. However, the adverse effects of weight gain and sedation are the usual limiting factors for use.  

Panic Disorder  

Mirtazapine may be used as an alternative treatment for PD.  

Anxiolytics  

Hydroxyzine  

Hydroxyzine blocks H₁ and muscarinic receptors. It may be considered in patients with no response to multiple treatment trials.  

Generalized Anxiety Disorder  

Hydroxyzine is considered as a weak anxiolytic in GAD. It has been found to be more sedating than benzodiazepines and Buspirone that can be useful for treatment of insomnia associated with GAD. 

Monoamine Oxidase Inhibitors (MAOIs)  

Panic Disorder  

Phenelzine is the most extensively studied MAOI in PD. It reduced the frequency and intensity of panic attacks and reduced anticipatory anxiety and associated depression. It may also lead to decreased avoidance of phobias. Their adverse effects, drug interactions, and dietary tyramine restrictions cause this group to be reserved for patients who fail SSRI, TCA or benzodiazepines.  

Social Anxiety Disorder  

MAOIs are given to SAD patients unresponsive to an alternative SSRI or a serotonin and norepinephrine reuptake inhibitor. Phenelzine and Moclobemide have been shown to be the most effective of this group. Studies have shown that they are effective in patients with SAD. However, their adverse effects, drug interactions, and dietary tyramine restrictions limit their use. 

Anticonvulsants  

Generalized Anxiety Disorder  

Pregabalin has been shown to improve somatic and psychic symptoms in patients with GAD. It also has proven efficacy for acute treatment and prevention of relapse.  

Panic Disorder  

Studies demonstrated that anticonvulsants show a significant benefit for patients with severe PD.  

Social Anxiety Disorder  

Gabapentin and Pregabalin have been demonstrated to decrease SAD symptoms. However, more studies are needed.  

Antipsychotics  

Generalized Anxiety Disorder  

There is good evidence that Quetiapine extended-release formulation is effective for the management of GAD and can be considered as adjunctive drug to SSRI or a serotonin and norepinephrine reuptake inhibitor for the treatment of resistant GAD. Although due to the likelihood of adverse effects like sedation, extrapyramidal symptoms (EPS), and tardive dyskinesia, their use is recommended only after safer alternatives have been exhausted.

Beta-Blockers  

Social Anxiety Disorder (Non-Generalized Subtype)  

Beta-blockers in SAD relieve autonomic symptoms (eg sweating, tremors) only. Their use should be intermittent and only administered until the individual’s performance confidence has returned. Among the beta-blockers, Atenolol is not recommended.  

Other Antidepressants  

Generalized Anxiety Disorder  

Agomelatine was found to be as effective as Escitalopram for the treatment of GAD.

For patients with GAD and other comorbid conditions (eg depressive or other anxiety disorders), it is recommended to treat the disorder that is more severe and in which it is more likely that treatment will improve overall functioning.  

Patient Education  

Patient education should be provided to all patients regardless of anxiety disorder or treatment type. It helps the patient and family to understand that the disorder is a real illness which requires treatment and support. It also addresses the patient's concerns and reassures and instills hope. It is important to talk to the patient beyond the somatic issues. It is also important to monitor the patient’s symptoms as well as functioning. Active monitoring may improve less severe presentations and avoid the need for further interventions. In panic attacks, explain to the patient that they are not life-threatening. The family is taught as well that the attacks can be disabling to the patient. Treatment options and risks versus benefits of both pharmacological therapy and psychosocial treatment are discussed.  

Cognitive Behavioral Therapy (CBT)  

CBT is a process that focuses on intervening in the thoughts and behaviors that have strong influence on the experience of emotion. It is the most effective form of psychotherapy for most anxiety disorders.  

In psychoeducation, the patient’s symptoms are identified, the basis of symptoms are explained, and the techniques for dealing with the symptoms are outlined. This may include workbooks and/or self-help materials. Problem solving is done in collaboration between the patient and the physician. It deals with identifying the problem, generating alternative solutions, selecting and implementing the initial approach, and monitoring of implementation and results. Continuous panic monitoring is also done.  

Cognitive restructuring involves investigating and reversing the fears that arise from misinterpretation of body sensations. This teaches the patient how to think about different outcomes of situations other than negative ones. In vivo exposure involves the actual exposure of the patient to their fear cues.  

In relapse prevention, a strategy in coping with problems that may arise in the future is developed. Booster sessions can be used to control or lessen the symptoms especially in patients where CBT has been effective. The combination of CBT and pharmacological intervention shows some effectiveness. However, further studies on benefit and cost of combined over single treatments are still lacking. 

Generalized Anxiety Disorder  

Relapse rates after discontinuing CBT are low compared to pharmacological therapy.  

Panic Disorder  

There is insufficient evidence to support whether CBT is superior to pharmacological therapy. Therefore, either therapy may be used as first-line treatment. Combination therapy with CBT and pharmacotherapy is preferred over multiple drug therapy in patients with inadequate response to initial pharmacotherapy. CBT is the psychotherapy of choice for PD. It is particularly useful during withdrawal of anxiolytics.  

Social Anxiety Disorder  

As an initial treatment option, individual CBT, especially in vivo exposure, has been shown to be superior to other forms of psychotherapy interventions. Cognitive techniques include restructuring and challenging maladaptive thoughts, while the behavioral component is typically in the form of exposure therapy. CBT treatment gains may be maintained longer than pharmacological therapy. Treatment gains tend to remain over no-treatment follow-up periods.  If there is only partial response to individual CBT, pharmacological therapy is considered. CBT may be given together with selective serotonin reuptake inhibitor (SSRI) if the patient had partial response with 10 to 12 weeks of SSRI therapy. In SAD, one may also use a CBT-based self-help book for support.

Distraction Techniques  

Distraction techniques such as listening to soothing music or thinking about pleasurable memory to replace anxiety-provoking thoughts can be done.  

Lifestyle Changes  

Lifestyle changes such as stress reduction, reduction of alcohol and caffeine consumption, avoidance of nicotine and drug use, regular exercise, and sleep hygiene may help in anxiety disorders.  

Mindfulness-based Interventions  

Mindfulness-based interventions focus on attention awareness of the present moment. It involves cultivating a non-judgmental attitude to reduce biases. It involves acquired relaxation and breathing techniques.  

Psychodynamic Psychotherapy  

Psychodynamic psychotherapy involves exploring the patient’s biopsychosocial development and the events before the onset of symptoms. The goal is to understand the reason for the anxiety based on the patient’s personality and development. It is an option for patients with SAD who refuse CBT and pharmacological approaches. However, there is less evidence showing its efficacy for the treatment of anxiety disorders.  

Relaxation Techniques and Biofeedback  

Relaxation techniques and biofeedback may be used to treat mild GAD. It is used to decrease arousal and control somatic manifestations. Studies have found that these techniques are more effective if combined with cognitive therapy. It may be combined with CBT in GAD treatment. Relaxation breathing, eg abdominal breathing, helps to control physiological overactivity.