Antidepressants Central nervous system depressants

Certain tricyclic compounds are found to be powerful stimulants, or antidepressants, to the central nervous system. Depressed individuals may respond with an elevation of mood, increased physical activity, mental alertness, and an improved appetite. Imipramine and amitriptyline hydrochlorides are good examples. 

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). 

Buspirone causes less psychomotor impairment than diazepam and does not affect driving skills. The drug does not potentiate the central nervous system depressant effects of conventional sedative-hypnotic drugs, ethanol, or tricyclic antidepressants, and elderly patients do not appear to be more sensitive to its actions. Tachycardia, palpitations, nervousness, gastrointestinal distress, and paresthesias may occur more frequently than with benzodiazepines. Buspirone also causes a dose-dependent pupillary constriction. Blood pressure may be elevated in patients receiving MAO inhibitors. A number of buspirone analogs have been developed (eg, ipsapirone, gepirone, tandospirone) and are under study. 

Interactions. Morphine (also pethidine and possibly other opioids) is potentiated by monoamine oxidase inhibitors. Any central nervous system depressant (including alcohol) will have additive effects. Patients recently exposed to neuromuscular blocking agents (unless this is adequately reversed, e.g. by neostigmine) are particularly at risk from the respiratory depressant effects of morphine. The effect of diuretic drugs may be reduced by release of antidiuretic hormone by morphine. Useful interactions include the potientating effect on pain relief of tricyclic antidepressants and of dexamfetamine. 

Avoid taking barbiturates, tricyclic antidepressants, antihistamines, central nervous system depressants, and OTC cold medications with MAOIs. 

Patients with coexisting cardiovascular and pulmonary conditions (e.g., ARDS, pulmonary infection, pulmonary aspiration) may be more susceptible to the toxic effects or complications of tricyclic antidepressant poisoning. The influence of chronic exposure to tricyclic antidepressants on the risks of an acute overdose is unclear. Tricyclic antidepressants interact with other central nervous system depressant drugs, which together may lead to increased central nervous system and respiratory depression. 

Central nervous system depressants are medications that suppress the transmission of information throughout the central nervous system. There are seven broad classifications of central nervous system depressants. These are sedative-hypnotics, general and local anesthetics (discussed later in this chapter), analgesics, narcotic analgesics (Chapter 16), anticonvulsants, antipsychotics, and antidepressants (discussed later in this chapter)... 

A. Haloperidol and droperidol potentiate central nervous system-depressant effects of opioids, antidepressants, phenothiazines, ethanol, barbiturates, and other sedatives. 

Clonidine should be used with caution in patients with cerebral, or coronary insufficiency, Raynaud s disease or throraboangitis obliterans, or with a history of depression. The hypotensive effect may be antagonised by tricyclic antidepressants, and enhanced by thiazide diuretics. Clonidine cause drowsiness and patients should not drive or operate machinery where loss of attention could be dangerous. The effect of other central nervous system depressants may be enhanced, withdrawal of clonidine therapy should be gradual as sudden discontinuation may cause rebound hypertension which may be severe. Agitation,... 

Hydromorphone should be used with caution if other central nervous system depressants are given concomitantly. These drugs are other opioids, general anesthetics, phenothiazine, tricyclic antidepressants, sedative-hypnotics, and other central nervous system depressants (including ethanol). 

Many patents have been issued on the use of pyrogaUol derivatives as pharmaceuticals. PyrogaUol has been used extemaUy in the form of an ointment or a solution in the treatment of skin diseases, eg, psoriasis, ringworm, and lupus erythematosus. GaUamine triethiodide (16) is an important muscle relaxant in surgery it also is used in convulsive-shock therapy. Trimethoprim (2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine) is an antimicrobial and is a component of Bactrin and Septra. Trimetazidine (l(2,3,4-trimethoxybenzyl)piperazine (Vastarel, Yosimilon) is used as a coronary vasodilator. l,2,3,4-Tetrahydro-6-methoxy-l-(3,4,5-trimethoxyphenyl)-9JT-pyrido[3,4- ]indole hydrochloride is useful as a tranquilizer (52) (see Hypnotics, sedatives, ANTICONVULSANTS, AND ANXIOLYTICS). Substituted indanones made from pyrogaUol trimethyl ether depress the central nervous system (CNS) (53). Tyrosine-and glycine(2,3,4-trihydroxybenzyl)hydrazides are characterized by antidepressant and anti-Parkinson activity (54). 

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

There is an increased risk for bone marrow suppression when levamisole or hydroxyurea are administered witii other antineoplastic dni. Use of levamisole witii phenytoin increases die risk of phenytoin toxicity. Pegaspargase may alter drug response of the anticoagulants. When procarbazine is administered with other central nervous system (CNS) depressants, such as alcohol, antidepressants, antihistamines, opiates, or the sedatives, an additive CNS effect may be seen. Procarbazine may potentiate hypoglycemia when administered witii insulin or oral antidiabetic dru . ... 

SSRIs are theorized to reduce the frequency of hot flashes by increasing serotonin in the central nervous system and by decreasing LH. Of the SSRIs, citalopram, paroxetine, and sertraline all have been studied and have demonstrated a reduction in hot flashes while treating other symptomatic complaints such as depression and anxiety.33 Venlafaxine, which blocks the reuptake of serotonin and norepinephrine, has demonstrated a reduction in hot flashes primarily in the oncology population.34 Overall, these antidepressant medications offer a reasonable option for women who are unwilling or cannot take hormonal therapies, particularly those who suffer from depression or anxiety. These agents should be prescribed at the lowest effective dose to treat symptoms and may be titrated based on individual response. 

Principal side effects are gastrointestinal and central nervous system symptoms, including drowsiness, dizziness, and diarrhea. Zolpidem may increase the depressant effects of other sedative drugs, such as the an-tipsychotics, tricyclic antidepressants, and antihistamines. 

We propose that the therapeutic efficacy of ECT may be related to activation of specific brain areas and the whole brain need not convulse for an antidepressant effect. It is possible that neural discharge in specific brain regions [Bolwig 1984], and not the convulsion, is the key factor for ECT s antide-pressive effects. External electrical stimulation as used for ECT may depolarize deep brain regions only by induction of convulsion. Local electrical brain stimulation in humans is not possible, of course ECT initiates massive discharge in the central nervous system [Lerer et al. 1984], and activation of no specific brain area has been proven to be the cause for ECT s therapeutic action. Local electrical stimulation of various brain regions for examination of antidepressive effect in animal models of depression would be a tedious and complicated task. 

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