Selective serotonin reuptake inhibitors benzodiazepines

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

Opioids, benzodiazepines, barbiturates, corticosteroids, dopamine agonists (e.g., amantadine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole), H2-receptor antagonists, anticholinergics (e.g., diphenhydramine, trihexylphenidyl), P-adrenergic blockers, clonidine, methyldopa, carbamazepine, phenytoin, baclofen, cyclobenzaprine, lithium, antidepressants (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors), and interleukin-2... 

FIGURE 37-2. Treatment alogorithm for GAD. SSRI = selective serotonin reuptake inhibitor BZ = benzodiazepine. (Reprinted, with permission, from reference 24.)... 

When treating anxiety one should of course first treat any reversible medical condition. When pharmacological treatment is necessary SSRI is most often drug of choice. Selective serotonin reuptake inhibitors are both effective and safe. Benzodiazepines that have been widely used are drugs with a relative high risk of adverse effects (see Chapter 4). Risks for dependence and abuse must always be considered for benzodiazepines. 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

Conflicting results (i.e., evidence is equivocal) , not investigated sufficiently BZD, benzodiazepines CBT, cognitive-behavioral therapy SSRl, selective serotonin reuptake inhibitors TCA, tricyclic antidepressants. 

The efficacy of beta-blockers in the symptomatic relief of anxiety in adults has been established in over a dozen controlled trials (Neppe, 1989). In a number of countries, beta-blockers have been licensed for the treatment of anxiety disorders. Somatic manifestations of anxiety such as palpitations, diaphoresis, and tremor, rather than core psychological symptoms, were particularly responsive to beta-blocker treatment. In comparative trials that included patients with severe anxiety and panic attacks, the antianxiety effect of beta-blockers was, however, somewhat less powerful than that of benzodiazepines (Lader, 1988), with the exception of a small trial that compared alprazolam to propranolol (Ravaris et ah, 1991). Head-to-head comparisons of beta-blockers and selective serotonin reuptake inhibitors (SSRIs) are lacking. Performance and stress-related anxiety that may affect public performers, such as musicians or people taking an examination or giving a speech, seems to be particularly suited for beta-blocker treatment (Lader, 1988). Beta-blockers may be given on an as-required basis 1-2 hours before the stressful situation. 

Antidepressants are as effective as benzodiazepines in the treatment of panic disorder. Moreover, antidepressants do not have the same risks of tolerance and dependency that are associated with benzodiazepine treatment. However, antidepressants take longer to work, so that significant improvement might not be observed until after a month of treatment. Although tricyclic antidepressants have been approved for the treatment of panic disorder, the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in its treatment has led them to become the favored treatment among antidepressant drugs. 

Traditionally, benzodiazepines and tricyclic antidepressants (TCAs) have been the most prescribed drug treatments for GAD. However, selective serotonin reuptake inhibitors (SSRIs), as well as selective serotonin and norepinephrine... 

Over the next 20 years, the benzodiazepines, TCAs, MAOIs, and beta-blockers were used to treat anxiety disorders. By the mid-1980s, up to 10% of all Americans were taking a benzodiazepine. In 1988, fluoxetine (Prozac) was introduced by Eli Lilly as the first selective serotonin reuptake inhibitor (SSRI) for the treatment of mood and anxiety disorders. Its success led to the development of several other SSRI drugs. Today, these drugs are the first line of drug treatment for most anxiety disorders. 

The prevalence of anxiety disorders has spurred the search for pharmacological ways to treat these pathologies. To date, doctors have found that drugs from two broad classes—the benzodiazepines and selective serotonin reuptake inhibitors. 

Kasper, S., and E. Resinger. Panic Disorder The Place of Benzodiazepines and Selective Serotonin Reuptake Inhibitors. European Neuropsychopharmacology 11 (2001) 307-321. 

Specific factors to consider are both psychiatric and physical contraindications. For example, bupropion is contraindicated in a depressed patient with a history of seizures due to the increased risk of recurrence while on this agent. Conversely, it may be an appropriate choice for a bipolar disorder with intermittent depressive episodes that is otherwise under good control with standard mood stabilizers. This consideration is based on the limited data suggesting that bupropion is less likely to induce a manic switch in comparison with standard heterocyclic antidepressants. Another example is the avoidance of benzodiazepines for the treatment of panic disorder in a patient with a history of alcohol or sedative-hypnotic abuse due to the increased risk of misuse or dependency. In this situation, a selective serotonin reuptake inhibitor (SSRI) may be more appropriate. 

A growing number of drugs are used that affect the many neurotransmitters in the brain benzodiazepines and others act on GABAergic transmission antidepressants, such as monoamine oxidase inhibitors and tricyclic antidepressants, are thought to increase the concentration of transmitter amines in the brain and so elevate mood—these will also act at peripheral nerve terminals, so interactions with them are a combination of peripheral and central actions. Levodopa (L-dopa) increases central as well as peripheral dopamine, and the newer class of psychoactive drugs, the selective serotonin reuptake inhibitors (SSRIs) of which the ubiquitous fluoxetine (Prozac) is best known, act in a similar way on serotonergic pathways. 

Disadvantages of the benzodiazepines include the risk of dependence, depression of central nervous system functions, and amnestic effects. In addition, the benzodiazepines exert additive central nervous system depression when administered with other drugs, including ethanol. The patient should be warned of this possibility to avoid impairment of performance of any task requiring mental alertness and motor coordination. In the treatment of generalized anxiety disorders and certain phobias, newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are now considered by many authorities to be drugs of first choice (see Chapter 30). 

Although they have been used for over 30 years, benzodiazepines are still widely prescribed in the treatment of anxiety disorders and other medical conditions. These drugs are classified as sedative-hypnotic agents, which depress or slow down the body. In the past 15 years, the development of the newer selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression and anxiety have pushed benzodiazepines aside as the first treatment choice because the SSRIs as a class of drugs have not yet been found to be addictive. 

Anorgasmia Failure to achieve orgasm. Usually psychological or interpersonal but can be iatrogenic due to antidepressants (particularly selective serotonin reuptake inhibitors), neuroleptics or benzodiazepines. 

ASA = aspirin NSAIDs = non-steroidal anti-inflammatory drugs, such as ibuprofen, naproxen, and diclofenac CNS stimulants include drugs such as pseudoephedrine, dextroamphetamine, theophylline, and caffeine MAO = monoamine oxidase CNS depressants include drugs such as benzodiazepines, barbiturates, and ethanol SSRIs = selective serotonin reuptake inhibitors, such as fluoxetine, sertraline, and paroxetine. Antidiabetic agents include drugs such as insulin, glipizide, glyburide, and metformin. 

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