Anxiolytic

Medications that are indicated for both anxiety disorders and depression. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are new generations of antidepressants. They have a much lower adverse effect profile than older antidepressants like monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressant (TCAs). Therefore, SSRIs and SNRIs are now the first-line agent in treating long term anxiety disorders, given their applications and significance in all 6 types of disorders.[5]

Benzodiazepines are used for acute anxiety and could be added along with current use of SSRIs to stabilize a treatment. Long-term use in treatment plans is not recommended. Different kinds of benzodiazepine will vary in its pharmacological profile, including its strength of effect and time taken for metabolism. The choice of the benzodiazepine will depend on the corresponding profiles.[5]

Benzodiazepines are used for emergent or short-term management. They are not recommended as the first-line anti-anxiety drugs, but they can be used in combination with SSRIs/SNRIs during the initial treatment stage. Indications include panic disorder, sleep disorders, seizures, acute behavioral disturbance, muscle spasm and premedication and sedation for procedures.

Useful in GAD but not effective in treating phobias or social anxiety disorders.[2]

Useful in treating GAD[2]

Olanzapine and risperidone are atypical antipsychotics which are also effective in GAD and PTSD treatment. However, there is also a higher chance of experiencing adverse effects than the other anti-anxiety medications.[5]

Propranolol is originally used for heart diseases. It can also be used to treat anxiety with symptoms like tremor or increased heart rate. They work on the nervous system and alleviate the symptoms as a relief.[5]

Both SSRIs and SNRIs are reuptake inhibitors of a class of nerve signal transduction chemical called neurotransmitters. Serotonin and norepinephrine are neurotransmitters that are related to nervous control in mood regulation. The level of neurotransmitters are regulated by the nerve through reuptake to avoid accumulation of the neurotransmitter at the endings of nerve fiber. By reuptaking the produced neurotransmitter, the level will go back down and ready to go back up upon excitation from a new nerve signal.[5] However the level of patients with anxiety disorders are usually low or their nerve fibers are insensitive to the neurotransmitters. SSRIs and SNRIs will then block the channel of reuptake and increase the level of the neurotransmitter. The nerve fibers will originally inhibit further production of neurotransmitters upon the increase. However the prolonged increase will eventually desensitize the nerve about the change in level. Therefore, the action of both SSRIs and SNRIs will take 4–6 weeks to exert their full effect.[2][5]

Benzodiazepines bind selectively to the GABA receptor, which is the receptor protein found in the nervous system and is in control of the nervous response. Benzodiazepine will increase the entry of chloride ions into the cells by improving the binding between GABA and GABA receptors and then the better opening of the channel for chloride ion passage. The high level of chloride ion inside the nerve cells makes the nerve more difficult to depolarize and inhibit further nerve signal transduction. The excitability of the nerves then reduces and the nervous system slows down. Therefore, the drug can alleviate symptoms of anxiety disorder and make the person less nervous.[5]

Selective serotonin reuptake inhibitors are the first-line anti-anxiety medications.[6] Serotonin is one of the crucial neurotransmitters in mood enhancement, and increasing serotonin level produces an anti-anxiety effect. SSRIs increase the serotonin level in the brain by inhibiting serotonin uptake pumps on serotonergic systems, without interactions with other receptors and ion channels. SSRIs are beneficial in both acute response and long-term maintenance treatment for both depression and anxiety disorder.

The common early side effects of SSRIs include nausea and loose stool, which can be solved by discontinuing the treatment. Headache, dizziness, insomnia are the common early side effects as well.

Sexual dysfunction is one of the adverse effects due to increasing level of serotonin but less common.

Withdrawal symptoms like dizziness, headache and flu-like symptoms (fatigue/myalgia/loose stool) may occur if SSRI is stopped suddenly. The brain is incapable of upregulating the receptors to sufficient levels especially after discontinuation of the drugs with short half life like paroxetine. Both Fluoxetine and its active metabolite have a long half life therefore it causes the least withdrawal symptoms.[6][9]

Tricyclic antidepressants are used as second line treatment for anxiety.

TCAs may cause drug poisoning in patients with hypotension, cardiovascular diseases and arrhythmias.

Barbiturates are powerful anxiolytics but the risk of abuse and addiction is high. Many experts consider these drugs obsolete for treating anxiety but valuable for the short-term treatment of severe insomnia, though only after benzodiazepines or non-benzodiazepines have failed.[11]

Antidepressant medications can reduce anxiety. The SSRIs paroxetine and escitalopram and SNRIs venlafaxine and duloxetine are USFDA approved to treat generalized anxiety disorder.

Benzodiazepines are prescribed to quell panic attacks. Benzodiazepines are also prescribed in tandem with an antidepressant for the latent period of efficacy associated with many ADs for anxiety disorder. There is risk of benzodiazepine withdrawal and rebound syndrome if BZDs are rapidly discontinued.[12] Tolerance and dependence may occur.[13] The risk of abuse in this class of medication is smaller than in that of barbiturates. Cognitive and behavioral adverse effects are possible.[14]

Benzodiazepines include: alprazolam (Xanax), bromazepam, chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), oxazepam, temazepam, and Triazolam.

Benzodiazepines lead to central nervous system depression, resulting in common adverse effects like drowsiness, oversedation, light-headedness. Memory impairment can be a common adverse effect especially in elderly, hypersalivation, ataxia, slurred speech, psychomotor effects.[2]

Selective serotonin reuptake inhibitors (SSRIs) are a class of medications used in the treatment of depression, anxiety disorders, OCD and some personality disorders.[15][16] SSRIs can increase anxiety initially due to negative feedback through the serotonergic autoreceptors, for this reason a concurrent benzodiazepine can be used until the anxiolytic effect of the SSRI occurs.

Serotonin–norepinephrine reuptake inhibitor (SNRIs) include venlafaxine and duloxetine drugs. Venlafaxine, in extended release form, and duloxetine, are indicated for the treatment of GAD. SNRIs are as effective as SSRIs in the treatment of anxiety disorders.[17]

Tricyclic antidepressants (TCAs) have anxiolytic effects; however, side effects are often more troubling or severe and overdose is dangerous. They are considered effective, but have generally been replaced by antidepressants that cause different adverse effects. Examples include imipramine, doxepin, amitriptyline, nortriptyline and desipramine.[18][19]

Mirtazapine has demonstrated anxiolytic effect comparable to SSRIs while rarely causing or exacerbating anxiety. Mirtazapine's anxiety reduction tends to occur significantly faster than SSRIs.

Monoamine oxidase inhibitors (MAOIs) are first-generation antidepressants effective for anxiety treatment but their dietary restrictions, adverse effect profile and availability of newer medications have limited their use. MAOIs include phenelzine, isocarboxazid and tranylcypromine. Pyrazidol is a reversible MAOI that lacks dietary restriction.[20]

Sympatholytics are a group of anti-hypertensives which inhibit activity of the sympathetic nervous system. Beta blockers reduce anxiety by decreasing heart rate and preventing shaking. Beta blockers include propranolol, oxprenolol, and metoprolol.[21][22] The Alpha-1 agonist prazosin could be effective for PTSD.[23] The Alpha-2 agonists clonidine and guanfacine have demonstrated both anxiolytic and anxiogenic effects.[24]

Buspirone (Buspar) is a 5-HT_1A receptor agonist used to treated generalized anxiety disorder. If an individual has taken a benzodiazepine, buspirone will be less effective.[25][26]

Pregabalin (Lyrica) produces anxiolytic effect after one week of use comparable to lorazepam, alprazolam, and venlafaxine with more consistent psychic and somatic anxiety reduction. Unlike BZDs, it does not disrupt sleep architecture nor does it cause cognitive or psychomotor impairment.[27][28]

Hydroxyzine (Atarax) is an antihistamine originally approved for clinical use by the FDA in 1956. Hydroxyzine has a calming effect which helps ameliorate anxiety. Hydroxyzine efficacy is comparable to benzodiazepines in the treatment of generalized anxiety disorder.[29]

Phenibut (Anvifen, Fenibut, Noofen) is an anxiolytic[30] used in Russia.[31] Phenibut is a GABA_B receptor agonist,[30] as well as an antagonist at α₂δ subunit-containing voltage-dependent calcium channels (VDCCs), similarly to gabapentinoids like gabapentin and pregabalin.[32] The medication is not approved by the FDA for use in the United States, but is sold online as a supplement.[33][34]

Mebicar is an anxiolytic produced in Latvia and used in Eastern Europe. Mebicar has an effect on the structure of limbic-reticular activity, particularly on the hypothalamus, as well as on all 4 basic neuromediator systems – γ aminobutyric acid (GABA), choline, serotonin and adrenergic activity.[35] Mebicar decreases noradrenaline, increases serotonin, and exerts no effect on dopamine.[36]

Fabomotizole (Afobazole) is an anxiolytic drug launched in Russia in the early 2000s. Its mechanism of action is poorly-defined, with GABAergic, NGF and BDNF release promoting, MT1 receptor agonism, MT3 receptor antagonism, and sigma agonism thought to have some involvement.[37][38]

Bromantane is a stimulant drug with anxiolytic properties developed in Russia during the late 1980s. Bromantane acts mainly by facilitating the biosynthesis of dopamine, through indirect genomic upregulation of relevant enzymes (tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AAAD)).[39][40]

Emoxypine is an antioxidant that is also a purported anxiolytic.[41][42] Its chemical structure resembles that of pyridoxine, a form of vitamin B₆.

Menthyl isovalerate is a flavoring food additive marketed as a sedative and anxiolytic drug in Russia under the name Validol.[43][44]

Some racetam based drugs such as aniracetam can have an antianxiety effect.[45]

Etifoxine has similar anxiolytic effects as benzodiazepine drugs, but does not produce the same levels of sedation and ataxia.[46] Further, etifoxine does not affect memory and vigilance, and does not induce rebound anxiety, drug dependence, or withdrawal symptoms.[46]

Alcohol is sometimes used as an anxiolytic by self-medication. fMRI can measure the anxiolytic effects of alcohol in the human brain.[47]