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Management of generalized anxiety disorders

By:   |   Jul 08, 2018   |   Views: 12   |   Comments: 0


Treatment for GAD fall into two main categories: psychological and psychopharmacological. Both pharmacotherapy and psychotherapy have been demonstrated to be effective in treating GAD. In current reviews and randomized placebo controlled trials have indicated that cognitive behavioral therapy (CBT), some SSRIs (paroxetine, esitalopram and sertaline) some serotonin noradrenalin reuptake inhibitors (SNRIs) (duloxetine and vanlafaxine), some benzodiazepines (alprazolam and diazepam), the 5-HT1A partial agonist buspirone, the antipsychotic trifluoperazine and antihistaminie hydroxizine are all efficacious.

The practitioner should first determine, before formulating a treatment that patient would benefit more from pharmacotherapy, psychotherapy or combination of both, in the view of severity of symptoms, presence of comorbidity, and presence of psychosocial stressors and patients preferences.


Psychotherapy is designed to help the patient to develop cognitive and behavioral strategies to effectively manage both cognitive and somatic symptoms that impede normal functionality. The major psychotherapeutic approaches to GAD are cognitive behavioral, relaxation, psychodynamic psychotherapy, supportive and insight - oriented therapies.

Cognitive behavioral therapy (CBT):

Cognitive behavioral therapy (CBT) has been demonstrated to be efficacious in relieving the symptoms of GAD in randomized controlled trails. Studies found recovery rates at a 6 month follow up between 50 % - 60 % among patients treated with CBT. Borkevec and Ruscio (2001) reviewed 13 controlled clinical trials of psychological therapy for GAD and found that CBT was associated with the lowest drop out and the largest within group and between group effect sizes relative to all other comparison condition. There are also data supporting the notion that CBT may have an additional impact in the comorbid conditions associated to GAD.

CBT consist of the patient working with a therapist trained in cognitive behavioral methods on a once per week basis over a six to twelve week period. The various form of CBT focus on symptom relief. More specifically treatment is focused on relief of cognitive, somatic and behavioral symptoms of GAD through the application of specified techniques. These techniques have included relaxation, systemic desensitization, applied relaxation (AR), cognitive restructuring (CR), worry exposure, stimulus control, response prevention, problem solving, pleasurable activity scheduling, interpersonal skill training and assigned worry time.


In addition to psychotherapies, physicians have numerous effective pharmacologic treatments. Recently developed drugs have been shown to be not only more effective than placebo, but also safer and more tolerable than other older medicines. Current medication options include benzodiazepines, buspirone, tricyclic anti depressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and venlafaxine among others.


Benzodiazepines, the most prescribed agent in the world, have the greatest degree of efficacy in the treatment of GAD of any medication class. These are one of the earliest approved treatments for anxiety disorders those have been used since 1960s replacing barbiturates because of their anxiolytic, anticonvulsant, and muscle relaxant properties. Benzodiazepines can be short acting (alprazolam and clonazepam), long acting (clorazepate and diazepam), both kinds   have been found to be efficacious in patient with GAD.

The effect of benzodiazepines are mediated through an activation of the γ- amino butyric acid (GABA) system at the GABAA receptor complex which leads to reduced neurotransmission throughout the central nervous system. Benzodiazepines have a rapid onset of symptom relief, most improvement occurs within the first few weeks of treatment. In trails comparing benzodiazepines with placebo, 65% to 75% of patients achieved moderate to marked improvement with benzodiazepines. However, their role in long term treatment of anxiety disorders is limited, given evidence that two third of those treated with benzodiazepines having remission. One drawback of benzodiazepines is that they do not reduce depressive symptoms and even in some cases exaggerate them.

Other potential side effects associated with benzodiazepines include sedation, fatigue, motor impairment, decreased learning ability and sleep disturbances. Benzodiazepines treated patients are also at risk for developing rebound anxiety and withdrawal symptoms. Abrupt withdrawal is associated with increased anxiety, sleep disturbances, agitation, headache, nausea, tremor and although (rarely) seizers.

5-HT1A partial agonist - Buspirone:

Buspirone, the only currently available azaspirone is the first non benzodiazepines anxiolytic approved for the treatment of GAD in 1986. Buspirone is a serotonin - 1A (5-HT1A) partial agonist, pharmacologically and structurally distinct from the other anxiolytic. It functions through a reduction of the firing of a serotonin affected nerve fibers by means of presynaptic serotonin agonism.

Buspirone is a potential alternative to benzodiazepine treatment in GAD. Response rates in between 60% to 80% have been reported at dosages ranging from 30 t0 60 mg a day in three divided dose. Despite comparable efficacy it tends to have delayed onset of action when compared to other treatments, often taking weeks or more to manifest efficacy. It is also associated with adverse effects such as dizziness, headache and nausea.


Tricyclic antidepressants (TCAs):

Controlled studies of the use of TCAs to treat GAD have produced data demonstrating their efficacy. Imparamine is the only tricyclic that has been demonstrated to be efficacious in treatment of GAD. Like Buspirone, it exhibits greater benefit to the cognitive dimension of the disorder than somatic. Imparamine works by inhibiting serotonin and / or nor epinephrine reuptake throughout the central nervous system.

Consequent use of TCAs may be complicated by adverse side effects like hypotension, edema, constipation, weight gain, sedation and cardiac conduction abnormalities.

Selective serotonin reuptake inhibitors (SSRIs):

SSRIs are currently the most widely prescribed treatment for anxiety disorders and are considered first line treatment. To date only paroxetine of this category of medication has been approved by the U.S. Food and Drug Administration (FDA) . SSRIs like TCAs have a slower time to onset compared to benzodiazepines but this medication at a dose of 20 - 50 mg per day was found to be more effective than benzodiazepines and placebo in reducing the symptoms of GAD, with a response rates of 40% to 70% and remission rates of 20% to 47%.

SSRIs tend to exhibit only mild adverse side effects such as nausea, sleep disturbances, dry mouth, headache and sexual dysfunctions.

Serotonin - nor epinephrine reuptake inhibitors (SNRIs):

Venlafaxine is a selective serotinergic and noradrenergic reuptake inhibitor (SNRI) that has been licensed for depression in UK since 1995. More recently, in 2001, a license for venlafaxine was approved for GAD. SNRIs bind with high affinity to serotonin and nor epinephrine transporters and inhibit the presynaptic reuptake of these neurotransmitters.

In an 8 week study of the efficacy of the extended release (XR) formulation of venlafaxine administrated in 75 mg and 150 mg daily dose, compared with buspirone and placebo, venlafaxine was associated with significantly greater reduction on the anxious mood item of the HAMA than both buspirone and placebo. Adverse effects associated with venlafaxine are generally mild and include dizziness, nausea, sexual dysfunction and dry mouth and most adverse effects substantially decrease during long term treatment with the drug.


Pregabalin is potentially new pharmacologic treatment for GAD. It is a structural analog of the inhibitory neurotransmitter gamma amino butyric acid (GABA) but is thought to exert its anxiolytic effects through binding in a state dependent manner to the alpha 2 delta subunit of voltage dependent calcium channels. In multi - centric clinical trials, Pregabalin appears to be generally well tolerated and has rapid onset of action (approximately one week) with comparable efficacy to benzodiazepines and lower discontinuation rate compared with other pharmacologic treatment in patients with GAD.


Unani system of medicine has described a well organized line of treatment plan in the management of diseases. The fundamental principle in the treatment is to restore the normalcy of patient, correction of imbalance Mizaj and to restore the balance of humors in the body by evacuation of excessive and deranged humors.

On the basis of general principles of treatment in Unani system of medicine we can adopt the following pattern of treatment in the management of Izterabe Nafsani Umoomi.

  1. Correction of sue mizaj.
  2. Elimination of the existing causes.
  3. Dietary management.

Correction of sue mizaj

Sue mizaj is considered as the basic cause of izterabe nafsani umoomi, this sue mizaj may appears in three different forms:

  1. Sue Mizaj haar sada
  2. Sue Mizaj safrawi
  3. Sue Mizaj saudawi

In sue mizaj haar sada there is excess hararat (heat) in the body especially in the brain, so to reduce haraarate dimagh some tadabeer (regimes) is used to produce baroodat (cold) and also some drugs possessing opposite effect on hararat such as musakkinate hararat (febrifuse) are used.

In sue mizaj maddi (safrawi and saudawi) restoration and normalization of humors is done by tanqiya (nuzj, istefragh) and ta'deele mizaj with their respective drugs. In nuzj (concoction) the akhlate raddiyah are altered in order to evacuate conveniently from the diseased organ by using drugs possesing properties of tahleel, taqtie, and talteef. Once the akhlate raddiyah is ready for elimination from the superficial and deeper structure of affected organ after a course of munzijat, istefragh (elimination) is brought into action with the help of mushilat. Mushilat are considered to facilitate the elimination of material out of body.

Ta'deele mizaj is related to restoration and normalization of physiological functions after eliminating the akhlate raddiyah from the affected organ. In this phase of the treatment the altered temperament is brought back to normal along with muqawwiyate dimagh drugs by using either alone or with tadabeer.

Elimination of existing causes

It is quite important to remove all the causative and predisposing factors of the disease such as, excessive fear, stress, excessive physical exertion, alcoholism, loneliness etc.

For this purpose, the following measures should be adopted:

  • A source of recreation should be provided like poetry, music, etc. for keeping patient happy.
  • Maintenance of adequate sleeping atmosphere.
  • The room should be airy, open and fragrant.
  • Correction of liver and spleen disorders.
  • Avoidance of alcohol consumption, smoking etc.
  • Abstinence from excess coitus.
  • Avoidance of heavy and strenuous work.
  • Avoidance of visiting overcrowded, dark and dirty places.
  • Avoidance of prolong stay in hot climate.
  • Proper care of heart should also be taken into consideration and cardiotonic and mufarrehe qalb (exhilarant) drugs should be used.

Dietary management:

  • Avoidance of all those items that are moallide sauda and safra (bile and black bile productive) like stale, salty and astringent food items.
  • Intake of light and delicious food items.
  • Use of murattib (emollient) diet such as barley water, milk, pumpkin, cucumber, leafy vegetables like spinach, lettuce, purslane etc.
  • Use of bilious concoctive fruits such as aalo bukhara, orange, lemon, ..etc.
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