Approach

The main goals in treating GAD are to improve symptoms of anxiety, improve quality of life, and improve functioning.

Education about GAD and its treatment options (psychoeducation) and active monitoring is the recommended first step in care in people with mild symptoms. Following this, first-line treatment options for GAD include:​​​​[48][49][50][65]​​​​​​[72][73]​​​[74]​​​​​

  • Psychological therapy (e.g., cognitive behavioral therapy [CBT])

  • Medication (e.g., selective serotonin-reuptake inhibitors [SSRIs] or serotonin-norepinephrine reuptake inhibitors [SNRIs])

  • The combination of psychological therapy and medication*.

*Note that some clinical guidelines, for example, Canadian and UK guidance, recommend a stepped care model for treatment of GAD, with psychologic therapy offered first-line, and medication only recommended if psychologic treatment has been unsuccessful, or from the start of treatment for those with marked functional impairment.​[50][65]

Data to guide clinicians on initial choice of treatment are limited.[75]​ For methodologic reasons, it is difficult to directly compare medication versus psychological therapy, although the current best available evidence suggests that medication and psychological therapy are broadly similar in efficacy for anxiety disorders in general.​​[21][74][76]​​​​​​​ The combination of medication and CBT is common in clinical practice, particularly for people with severe GAD, although evidence on this specific to GAD is limited. There is some evidence to suggest that the combination of psychological treatment (CBT) plus medication performs better than psychological treatment alone, at least in the short term.[77][78]​​​​​ The beneficial effects of CBT may last longer than those of medication.[21]

Based on the above uncertainty, treatment selection should be individualized, and involves a shared decision-making process between patient and clinician.[21] When constructing a treatment approach, consider patient preference, severity of GAD, potential adverse effects, past treatment history, comorbid psychiatric conditions, and treatment availability.​​​[49]​​[65]​ Clinicians should consult local treatment guidelines, which vary internationally.​​[49][50]​​​[65][73]

As a general guide, consider offering:

  • Watchful waiting and/or psychoeducation or CBT for those with mild anxiety symptoms

  • CBT or medication (or both) for those with moderate anxiety symptoms

  • CBT plus medication for those with severe or treatment-resistant anxiety.

A number of factors may suggest a need to prioritize initial treatment with medication, including previous nonresponse to psychological therapy, chronic course of illness, high complexity of illness, and depression comorbidity.[21] There is evidence that antidepressants are more effective in those with severe GAD compared with mild GAD. The implications of this are that the benefit-risk ratio may be less favorable for patients with milder GAD, although the practical implications (i.e., threshold for effectiveness) are unclear.[79]

Psychotherapy and other nondrug treatments

Psychotherapy (face-to-face, delivered electronically, or a combination of the two approaches) is particularly useful for patients who cannot tolerate or do not want medication. In practice, psychotherapy ranges from low-intensity interventions (e.g., bibliotherapy) to high-intensity therapies with a specialist therapist; as a general guide, the intensity of treatment increases with increasing severity of GAD.[21]​ According to one large meta-analysis of 41 studies, which examined the efficacy of various types of psychological therapies for GAD (but mainly CBT), the overall effect size for psychological treatment corresponded to a number needed to treat (NNT) of approximately 2.[80]

Follow-up studies indicate an enduring effect of psychological treatments beyond the active treatment period.[81]

Cognitive behavioral therapy (CBT)

CBT is considered the first-line option for psychotherapy for GAD. There is a large body of evidence to suggest that it significantly reduces symptoms of GAD, compared with psychological placebo or waiting-list control.[82][83]​​​​[84][85]​​ One review of 87 studies concluded that 47% of patients with GAD achieved symptom reduction to within normative levels following treatment with CBT.[86]​ CBT is associated with enduring benefits on symptoms of GAD persisting up to 12 months after treatment, according to another review.[87]

CBT may be especially helpful for generalized anxiety in later life, although whether CBT is superior to other commonly available psychological treatments is unclear.[88][89][90][91]​​ In practice, CBT may be difficult to access due to a lack of qualified practitioners.

Computer/smartphone-assisted and internet-based interventions may help facilitate access to CBT for people such as those who live in remote locations, or for those on waiting lists in areas where there are long waiting lists for face-to-face treatment. Studies have demonstrated efficacy of internet-based CBT delivered by individually administered media interventions, although study quality is variable, and frequently low.[92][93]​​​​​​ Digital interventions may be more appropriate for those with mild or subthreshold symptoms of anxiety, and for those who are especially motivated to improve their symptoms.[94][95]​​​​​ Guided interventions (with input from a therapist via email or face-to-face, or via a computer-driven interaction) are associated with larger effect sizes than nonguided interventions.[93][96][97]​​​​[98][99][100]​​ [ Cochrane Clinical Answers logo ] ​​​​​​ There is also evidence for efficacy of videoconferencing psychotherapy.[101]​​

Other nondrug therapies

A number of other nondrug therapies are also options for GAD, which may be used alone or in combination with CBT depending on the specific clinical scenario.

  • Mindfulness or meditation training may be considered as a standalone option for patients who are unable and/or unwilling to do psychotherapy, or can be used as an adjunct to CBT.[102][103][104][105][106]​​[107]​​​

  • Applied relaxation training can be a useful treatment.[80][108][109]​​​​ UK guidelines recommend that applied relaxation may be used to treat GAD as a standalone intervention, or it may also be considered as an adjunctive treatment. Treatment should be manualized and delivered by a trained practitioner.[65]​ 

  • Attention/perception modification is effective for treating GAD in university and college students.[105]

  • Both short- and long-term psychodynamic psychotherapy have also been found to be effective.[110][111][112] [ Cochrane Clinical Answers logo ]

  • Sleep hygiene measures may be beneficial. Counsel patients to improve sleep hygiene by going to bed and waking up at the same time each day, abstaining from or minimizing their use of alcohol, and avoiding caffeine after 3 p.m. Advise the patient to get out of bed if they are unable to fall asleep, in order to avoid developing negative associations with being in bed.[113][114]

  • There is some evidence that exercise interventions can reduce anxiety symptoms, with high-intensity programs showing greater effects than low-intensity programs.[115][116][117][118]

  • Yoga is associated with improved anxiety symptoms in the short term, according to one meta-analysis.[119]

  • Self-help treatments, such as books or self-help manuals, have been shown to be more effective than waiting list or placebo.[120][121]

  • Other treatments for which there is some evidence of effectiveness include interpersonal therapy, supportive therapy, problem-solving therapy, and acceptance and commitment therapy.[122][123][124]​ However, these should not be used first line as there is more evidence supporting CBT.

  • One meta-analysis concluded that motivational interviewing in addition to CBT for anxiety disorders improves treatment outcome, compared with CBT alone.[125]

  • Anecdotally, people with GAD may report benefit from smartphone apps that teach mindfulness/relaxation skills, although there is insufficient evidence to recommend specific apps given that the majority have not been studied within randomized controlled trials (RCTs).

Psychotherapy: relapse prevention

Although CBT is associated with an enduring positive effect over time, relapse (e.g., 1-2 years after discontinuation of CBT) is not uncommon. Maintenance CBT (either in-person or remotely) over the course of several months may be protective, based on studies in other anxiety disorders.[126][127]​​​ "Booster" CBT sessions for those who experience a recurrence of symptoms may improve outcomes.[87]

Pharmacotherapy

Pharmacotherapy for GAD is associated with a reduction in anxiety symptoms resulting in meaningful improvements in quality of life and functioning.[128]​ SSRIs, in particular sertraline or escitalopram, are the first-line pharmacologic treatment.​​​[49][65]​​[129]

Other options include:

  • Mirtazapine (an atypical antidepressant)

  • SNRIs (e.g., duloxetine, venlafaxine)

  • Buspirone (a non-benzodiazepine anxiolytic)

  • Pregabalin (an anticonvulsant)[73][130]

  • Benzodiazepines (e.g., diazepam, clonazepam)

  • Quetiapine (an atypical antipsychotic)

  • Tricyclic antidepressants (TCAs; e.g., clomipramine, imipramine).

Medication selection

Base drug selection on the severity of illness/degree of distress, presence of other mental or physical health conditions, past treatment history, substance misuse profile, patient preference, and adverse-effect profile.[131] When exploring past treatment history, it is important to establish whether a therapeutic trial of a particular drug was attempted, if that treatment was deemed ineffective. Sometimes, a past trial may have been too short, or a drug may have been initiated at a subtherapeutic dose that was not titrated upward.[132]

Dose titration

Monitoring for adverse effects, modifying the dose, and switching medications may improve efficacy and patient adherence (e.g., some antidepressants may cause restlessness, which can worsen anxiety symptoms).[133]​ Furthermore, patients with anxiety may be more susceptible to drug adverse effects. The recommended starting dose of antidepressants is typically half of the recommended dose for depression, although the therapeutic dose is the same or even higher.[49] Response to antidepressant treatment for GAD is relatively slow. The anxiolytic effects of antidepressants should typically begin around 2-4 weeks after initiation, but improvement may continue for weeks to months following this.[134]​ Maintain the initial starting dose for up to 4 weeks before assessing the treatment response.[49] Benefit should be seen by 12 weeks at a therapeutic dose. If this is not the case, try an alternative.​[48][49]​​

Evidence for GAD pharmacotherapy

Several guidelines make suggestions with variations in the detail regarding choices of pharmacotherapy for GAD.[48][49][73]​​​​ Few RCTs have directly compared pharmacotherapy options for GAD. The recommendations in this topic are based in part on a comprehensive and influential network meta-analysis of pharmacotherapies conducted in 2019, along with clinical experience with these drugs.[130] The network meta-analysis included 89 trials and 25,441 patients randomly assigned to 22 different active drugs or placebo. The main conclusions were:

  • Duloxetine, venlafaxine, escitalopram, and pregabalin were more effective and had better acceptability than placebo.

  • Mirtazapine, sertraline, fluoxetine, and buspirone were also effective and well tolerated, but these conclusions were based on fewer studies and small sample sizes.

  • Paroxetine, benzodiazepines, and quetiapine were efficacious as measured by the Hamilton Anxiety Rating Scale (HAM-A), but poorly tolerated compared with placebo.[130]

Information about the long-term effects of these drugs in GAD is limited.

Psychotherapy and other nondrug therapies may be used in addition to pharmacotherapy.

First-line pharmacotherapy:

  • SSRIs are considered first-line pharmacotherapy for GAD, given the available evidence regarding efficacy and adverse effects.​​​[49][65]​[129]

  • Of the SSRIs, escitalopram and sertraline are recommended for GAD by the author of this topic, based on systematic review and meta-analysis data that directly compared pharmacologic treatments for GAD, as well as on UK-based guidance from the National Institute of Health and Care Excellence (NICE). NICE recommends sertraline as having the highest acceptance, risk-to-benefit ratio, and cost-effectiveness profile of pharmacologic treatment options for GAD.[65]​​[130][135]​​​ Paroxetine is poorly tolerated; patients may experience breakthrough anxiety symptoms, and there are also concerns about discontinuation syndromes.

  • SSRIs have demonstrated efficacy in treating GAD in older patients, children, and adolescents, and have demonstrated efficacy both in short-term treatment and in preventing relapse of GAD.​[48][73][136][137][138][139][140][141]

  • For patients who are unable to take an SSRI (e.g., due to bleeding risk), one option is to offer mirtazapine. Advantages of mirtazapine include its relative safety in older people, and lower rate of drug-drug interactions compared with other pharmacologic treatment options for GAD. However, note that there are very few clinical trials assessing mirtazapine for anxiety disorders, and for GAD in particular.[142]

Second-line pharmacotherapy:

  • SNRIs are typically considered a second-line option for GAD, and as such may be considered for patients who have not tolerated or not experienced symptomatic improvement with one to two SSRIs.[49]

  • The available evidence suggests that they are effective compared with placebo and compared with other pharmacologic treatment options for GAD.[130][143][144][145]​​​​​​ However, in the author's clinical experience they may be somewhat less well tolerated than SSRIs.

  • Venlafaxine and duloxetine are preferred, based predominantly on the results of a large 2019 network meta-analysis that concluded that both drugs were more effective and had better acceptability than placebo, backed by a substantial body of evidence.[130] 

Third-line pharmacotherapy:

  • If there is no or minimal response to first- or second-line treatment options, primary care clinicians should typically consider seeking a specialist opinion from secondary care at this point, if not done already.

  • Buspirone or pregabalin may be considered third-line options for GAD.[146][147][148]​​​​​

  • Buspirone is considered effective in some patients.[146] It is also nonaddictive, which is beneficial in patients with a history of drug or alcohol misuse. However, nausea is common and may limit its use. Recent benzodiazepine use is thought to reduce its efficacy.[131]

  • Pregabalin can be used alone or as an augmentation agent with other medications where there has been a partial response to the initial choice of treatment.[149]​ One systematic review found that, in patients with GAD, pregabalin was superior to placebo and comparable to benzodiazepines in clinical response, with a lower dropout rate than with benzodiazepines.[150]​ However, use pregabalin with caution as it may cause renal impairment, especially in patients with risk factors for renal impairment (e.g., older age, substance misuse, concomitant medications such as antihypertensives and some antibiotics), and because of the ongoing risk of confusion.[151]​ Pregabalin is eliminated principally by renal excretion. Dose adjustment is required in people with compromised renal function. Pregabalin has the potential to be addictive.[152]​ Pregabalin should be avoided in patients taking opioids, due to an increased risk of sedation, and somnolence and death in overdose. Pregabalin is designated a controlled drug in some countries in order to reduce the increasing number of deaths and dependency associated with its misuse.[153]

Further-line pharmacotherapy (note that the following treatments should typically be initiated under specialist guidance only):

TCAs

  • Evidence for the effectiveness of TCAs in GAD is scarce, dated, and suggests imipramine or clomipramine are the TCAs of choice.[129][154][155]

  • Careful consideration of risk in overdose and cardiac adverse effects is required. In practice, safety concerns around TCAs largely limit their use, including the relatively high fatality risk in overdose.[22]

Quetiapine

  • Quetiapine may be considered but carries the risk of metabolic and other significant adverse effects.[156]

  • Quetiapine monotherapy has been found to be more effective than placebo in the treatment of GAD in two systematic reviews and one meta-analysis.[130][156][157]​ These data showed that quetiapine may be poorly tolerated by patients; patients treated with quetiapine had an increased risk of all-cause discontinuation, discontinuation due to adverse effects, weight gain, and metabolic syndrome. Quetiapine can affect the QTc interval and can increase the risk of metabolic syndrome. Do not offer antipsychotics such as quetiapine as initial treatment for GAD.

  • Note that initial prescription of antipsychotics within primary care is not recommended according to UK guidance, although in practice antipsychotics may be prescribed under shared care arrangements.​[65]

Benzodiazepines

  • While benzodiazepines may be effective in the short term, their continued use is associated with important harmful adverse effects (e.g., falling more often; memory impairment, particularly new learning; increasing the risk of accidents; and dependence with a troublesome withdrawal syndrome).[158][159][160]

  • Some treatment guidelines, such as those from NICE in the UK, recommend against the use of benzodiazepines for GAD in primary or secondary care, except as a short-term measure during crises.[65]​​[Evidence A]​​[Evidence A]​​​​​​ However, some clinicians consider benzodiazepines to be a useful part of the treatment armamentarium for a subsection of patients with refractory anxiety disorders in a limited number of additional scenarios.[161][162]​​​

  • ​Cautious benzodiazepine use is recommended as a second- or third-line agent for management of anxiety disorders according to some treatment guidelines.[48][50][73]​​​​​

  • The effectiveness of long-term use for GAD is unclear, and the development of tolerance may occur.[49][163][164]​​​​​

  • The key issue for clinicians and patients is risk versus benefit. Benzodiazepines are more effective in a population with higher baseline severity.[165] They may also have a more favorable adverse effect profile in the management of treatment-refractory anxiety disorders, compared with atypical antipsychotics.[49] They do not generally affect the QTc interval, but they can cause respiratory depression and death in overdose, and/or when used in combination with alcohol or opioids.[166][167]

  • Avoid benzodiazepines if the patient has a history, or is at risk, of substance misuse.[49]

  • Their mortality in overdose is high when used concurrently with opioids.[168]

  • Benzodiazepines should typically only be used on a short-term basis (e.g., 2-4 weeks).[49] Occasionally they are used on a long-term basis to treat refractory anxiety. Long-term treatment with benzodiazepines should be rare, supervised, made with caution, and based on careful consideration of the anticipated risks and benefits of benzodiazepines for the individual patient; specialist input (e.g., from a psychiatrist or addiction specialist) is advisable. Patients using benzodiazepines long term should be regularly offered the opportunity to gradually withdraw from long-term use; treatment at the lowest effective dose is recommended.[169]

  • Benzodiazepines have a rapid onset of action and are generally well tolerated. Physiologic dependence can occur in as little as 2-4 weeks. Abrupt discontinuation or rapid tapering schedules can increase risk for withdrawal symptoms (e.g., dizziness, irritability, nausea, sweating, tremors, rebound anxiety, and seizures).

  • Longer-acting agents (e.g., diazepam, clonazepam) may be preferable to minimize interdose rebound anxiety.

Duration of treatment

  • Very few data are available on the optimal duration of treatment. Once a good therapeutic response is achieved, continue treatment for at least 1 year, after which a trial of discontinuation may be considered. This advice is based on expert opinion and systematic review and meta-analysis data that suggest that treatment with antidepressants for at least 1 year is associated with reduced rates of relapse, and is well tolerated.​​​​[48][50][73][170]

  • After this time, the patient and prescriber can discuss whether or not to continue, based on adverse effects and other considerations. For example, the patient may wish to try coming off the medication if their level of life stress has decreased.[40]​​

  • If there is agreement to reduce and stop the antidepressant, do so slowly and carefully monitor for the recurrence of symptoms.

  • There is limited evidence on effect and safety of different medication discontinuation strategies for anxiety disorders, meaning that evidence is lacking on the optimal rate of discontinuation, as well as on the presence of psychological support during discontinuation.[171]

  • As a general guide based on expert opinion, discontinue the drug by no more than a quarter of the dose each month, but note that some patients may require more gradual rates of withdrawal over several months.[22]

  • If relapse occurs during or after discontinuation, clinical practice is to reintroduce treatment, although the evidence base to support this is lacking.

  • "Booster" sessions of CBT may be considered if patients experience a relapse after a successful course of CBT.​[87][132]

Comorbid major depression

  • Treatment is similar to that for patients without depression. For more detailed information, see Depression in adults.

  • However, buspirone and pregabalin are not recommended for patients with comorbid major depression.

  • SSRI and SNRI treatment of anxiety with major depression has evidence for effectiveness.[172]

  • CBT directed toward GAD has the additional advantage of improving depressive symptoms.[85]

  • Closely monitor patients with comorbid major depression who are treated with sedatives (e.g., benzodiazepines), sedating medications, or TCAs for suicidal risk.[173]

  • Patients with severe depression and suicidal ideation may require hospitalization while therapy takes effect. See Suicide risk mitigation.

Refractory GAD

  • There is little to no evidence to indicate optimal treatment for symptoms refractory to the above treatments.

  • Consider switching to an alternative drug, combining drug therapy with psychotherapy such as CBT, or combining two medications from different drug classes (if there are no contraindications). Obtain patient consent and agree outcome measures.[49]

  • Stop treatments that are not working, and ask the patient which symptoms concern them the most. Then agree a reasonable end point (using scales or other agreed outcomes) and treat with an alternative medication, or with combined drug and psychotherapy (e.g., CBT), for 12 weeks. If a particular kind of treatment is not effective, stop it and try another strategy until the most efficacious therapy for the individual patient is found.[49]

  • Consult a specialist before combining medications.

Children and adolescents

For children with mild symptoms, treatment options include psychoeducation, anxiety management training, and CBT.[58]​ Medication is typically considered as a second-line option for children with moderate to severe anxiety whose symptoms do not improve (or only partially improve) with psychotherapy.[58][174]​​ Clinicians should follow local service arrangements, but typically, pharmacotherapy should be initiated and prescribed only under the supervision of a specialist mental health service for children and young people.

Resources to support children and parents include:

Psychotherapy

CBT is recommended first line for moderate or persistent GAD.[58][174]​​​​ The available data suggest that CBT is an effective treatment for anxiety in children.[175][176][177]​​​​​​ One 2020 Cochrane review reported that compared with children on waiting lists or receiving no treatment, CBT increased the probability of a child with a primary anxiety diagnosis achieving remission following treatment, although when compared with "treatment as usual" (which included access to pharmacotherapy and other types of psychotherapy) no statistical difference in efficacy was found.[178]​ CBT focused on the primary anxiety disorder also improves comorbid mood and/or behavioral disorders in children and adolescents.[179] There is also good evidence for the effectiveness of e-therapy (i.e., computerized CBT) in children (such as SPARX).[180] SPARX Opens in new window​​​​​ In the UK, NICE recommends a number of named guided self-help digital CBT technologies that may be considered as an initial treatment option for children (ages 5-18) with mild to moderate symptoms of anxiety or low mood.[181]

CBT can be offered directly to children, or to the parents or caregivers of younger children. For children ages 5-7, there is evidence to suggest that parent-only CBT may be an effective alternative to CBT involving both parent and child.[182]​ Equality and diversity should be considered in the provision of CBT; for example, it can be modified for children and young people with autistic spectrum disorder.[183] Of note, many clinical trials involving children and adolescents consider multiple anxiety disorders or symptoms, with or without depression, rather than specifically investigating the population of children with GAD.

Pharmacotherapy

Prescribing in this age group is complicated by a relative lack of high-quality trial data on adverse effects and withdrawal risks, including a potential risk of suicidality with some pharmacologic treatments.[49]

Psychotropic medication can be considered by a specialist mental health service for children whose symptoms do not improve with CBT. The combination of pharmacotherapy (with an SSRI) and psychotherapy (with CBT) has been shown to improve outcomes.[184]

SSRIs and, to a lesser extent, SNRIs are the pharmacologic treatment of choice in children, given their favorable risk-benefit ratio compared with other antidepressants.[58][185]​​​ Both SSRIs and SNRIs are effective for reducing childhood anxiety symptoms, compared with placebo, although the benefit is small.[177][186]​ One meta-analysis found that for pediatric patients with anxiety disorders (including GAD), both SSRIs and SNRIs resulted in a clinically significant improvement in anxiety symptoms compared with placebo, but that SSRIs were associated with a greater and more rapid symptomatic improvement than SNRIs.[187] SSRIs are associated with a small increased risk of suicidality in young people under the age of 24. The number needed to harm (NNH) has been estimated at 143, compared with a number needed to treat (NNT) of 3.[188]​ Close observation for suicidality is recommended, especially in the early weeks of treatment, and following dose adjustments.[58]​ There is limited evidence on the effects of other drugs such as antipsychotics, benzodiazepines, buspirone, hydroxyzine, or pregabalin for children and adolescents with GAD.[189]

Clinically significant improvement with SSRIs may not be apparent until 6-8 weeks into treatment, with maximal benefit occurring at around 12 weeks.[187] SSRIs should be continued for at least 6 months if they are found to be effective, or for at least 1 year if used to treat a relapse of GAD.[190]

Pregnancy

The goal of treatment is symptom remission. Treatment may be pharmacologic or nonpharmacologic; in either case, use of a validated screening tool to monitor for response to treatment or remission of anxiety symptoms is recommended.[191]

Nonpharmacologic treatment (in particular CBT) is recommended first line, particularly for those with mild to moderate anxiety.[49]​​[191][192]​​​​​​​ Much of the evidence for management of pregnant and postpartum women relates to anxiety as a mixture of symptoms, which can span multiple International Classification of Diseases (ICD) or Diagnostic and Statistical Manual (DSM) diagnostic categories.

If CBT is not available, consider other types of psychotherapy (e.g., psychodynamic counseling). UK guidelines recommend that applied relaxation may be used to treat GAD.[65]​​

Psychological therapies can be delivered in person or remotely. One meta-analysis found that online "eHealth" interventions significantly reduced anxiety scores in women with perinatal anxiety who received the intervention, compared with controls.[193] There is also evidence for the efficacy of video-conferencing psychotherapy and smartphone mental health interventions in treating anxiety.​[98][101]

Medication should be considered for women with severe or disabling anxiety.​​​[49][191]​​​ The decision whether to start pharmacologic treatment during pregnancy must balance the potential for iatrogenic harm to the fetus (given that antidepressants all cross the placenta) with the potential harm for the mother and fetus from untreated psychiatric illness. In the US, such discussions are frequently carried out by the patient’s obstetrician; obstetricians in the US may seek further specialist treatment advice from Perinatal Psychiatry Access Programs where available.[191]​ In other locations (e.g., the UK) clinicians should consult a specialist with experience in perinatal mental health when selecting the most appropriate drug for patients. Treatment is the same regardless of whether comorbid major depression is present or absent. 

In general, SSRIs are considered first-line medications for the treatment of both perinatal anxiety and depression.[191] The American College of Obstetricians and Gynecologists (ACOG) note that treatment decisions should be guided by any previous response to treatment but that, for those who have not taken a medication in the past and for those for whom other medications were not effective, sertraline is often preferred in the perinatal period due to its extensive and reassuring safety evaluation in the medical literature. Escitalopram is a reasonable alternative based on efficacy and acceptability data in the general population.[191]​​

There is little controlled trial evidence of treated and untreated women.[194] Some research has demonstrated that women with psychiatric illness during pregnancy are less likely to receive adequate prenatal care; more likely to use alcohol, tobacco, and other substances known to adversely affect pregnancy outcomes; and more likely to have a preterm delivery.[195] SSRIs can shorten the duration of pregnancy slightly in women with GAD, and are associated with hypertensive disease of pregnancy and use of minor respiratory interventions in the newborn.[196] SSRIs are also associated with a small increased risk of postpartum hemorrhage when used in the month before delivery.[197]​ Maternal benzodiazepine use is associated with cesarean delivery and use of ventilatory support for the newborn.[196] Evidence of a relationship between antidepressant treatment during pregnancy and a risk of autistic spectrum disorders (ASDs) in offspring is mixed, with some studies showing an association between maternal antidepressant use during pregnancy and a slightly increased risk of ASD in the child. Other studies show increased risk of ASD in children of mothers with a prenatal psychiatric disorder and no antidepressant use.[198][199][200]​​ Studies investigating whether pregabalin is associated with an increased risk of major congenital malformations have yielded conflicting results and are underpowered; pregabalin should only be used where the risk-to-benefit ratio is favorable and after shared decision making.[201]

​If a woman becomes pregnant while on pharmacotherapy, discuss the options of stopping the medication gradually and switching to a psychological intervention, continuing with medication, and combining medication with a psychological intervention.[53] Depending on the speciality and experience of the decision-maker, clinicians should consider consulting a psychiatrist about the risks and benefits of continuing drug therapy. Data suggest that continuing SSRIs during pregnancy may prevent risks associated with anxiety symptoms and comorbid depression.[202] Involve the woman in the consultation process and take her preferences into consideration. 

This is a fast-changing area; updated information about potential harms from antidepressants and other pharmacologic therapy in pregnancy is available. MotherToBaby Opens in new window

Newborns should be monitored for the effect of psychotropic medications taken in pregnancy, and breast-feeding should be encouraged.[53] Consult a specialist with experience in perinatal mental health and consult a local drug formulary when selecting the most appropriate drug for patients who wish to breast-feed. 

Additional nondrug therapies such as applied relaxation, meditation training, sleep hygiene education, exercise, and self-help books/manuals may be used during pregnancy. Self-help treatments, such as books or manuals, have been shown to be more effective than wait-list or placebo.[120][121]

Anxiety symptoms not meeting DSM-5-TR criteria

Anxiety is normal and universal.[49] However, patients who have distressing or troubling generalized worry but who do not fully meet the diagnostic threshold set by the Diagnostic and Statistical Manual of mental disorders, 5th edition, text revision (DSM-5-TR) for GAD may benefit from the same treatments used for GAD, especially psychotherapy, meditation training, and sleep hygiene education.[203] Consult a psychiatrist for patients who have anxiety symptoms not clearly meeting DSM-5-TR criteria and who have mixed psychiatric symptoms (e.g., depression, substance misuse).

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