Clonidine antidepressants

Some alicyclic 1,2-diamine derivatives have recently been shown to have interesting CNS properties. For example, eclanamine (34) is an antidepressant with a rapid onset of action. The reasons for its potency are not as yet clear but pharmacologists note that the drug desensitizes adrenergic alpha-2 receptors and antagonizes the actions of clonidine. The synthesis of eclanamine starts with attack of cyclopentene oxide (30) by dimethylamine (to give 31). This product is converted to the mesylate by reaction with sodium hydride followed by mesyl chloride. Attack of... 

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... 

Medications (analgesics, anticholinergerics, calcium channel blockers, clonidine, diuretics, phenothiazines, tricyclic antidepressants, iron supplements, calcium- and aluminum-containing antacids)... 

Pharmacodynamic interaction clonidine acts as an agonist at a2-receptors, and these TCAs block this receptor to varying degrees the result is an increase in blood pressure either avoid this interaction by choosing another antidepressant or increase the dose of clonidine. 

This interaction is the same as the one when clonidine is combined with TCAs however, mirtazapine is a more potent a2-receptor blocker than the TCAs avoid this interaction and choose an alternative antidepressant without a2-blocking effects. 

The proposed mechanism of ADHD pharmacotherapy is to modulate neurotransmitters in order to improve academic and social functioning. Pharmacologic therapy can be divided into two categories stimulants and non-stimulants. Stimulant medications include methylphenidate, dexmethylphenidate, amphetamine salts, and dextroamphetamine, whereas non-stimulant medications include atomoxetine, tricyclic antidepressants (e.g., imipramine), clonidine, guanfacine, and bupropion. 

A number of non-hormonal therapies have been studied for symptomatic management of vasomotor symptoms, including antidepressants [e.g., selective serotonin reuptake inhibitors (SSRIs) and venlafaxine], herbal products (e.g., soy, black cohosh, and dong quai), and a group of miscellaneous agents (e.g., gabapentin, clonidine, and megestrol). The choice of therapy depends on the patient s concomitant disease states, such as depression and hypertension, and the risk for potential adverse effects. 

Overall, non-hormonal therapies are less effective in treating vasomotor symptoms than HRT but do offer an important option for women experiencing menopausal symptoms who cannot or are unwilling to take HRT. The antidepressants gabapentin and clonidine have the best evidence for efficacy of all the non-hormonal options and should be considered first as an alternative to HRT. The most important considerations in choosing an alternative therapy are the patient s comorbidities and the efficacy and safety of the medication. 

Centrally acting agents (clonidine, methyldopa, and reserpine) Spironolactone a-Blockers Lipid medications Gemfibrozil Antidepressants... 

Unfortunately, the mood stabilizers have not proved very helpful in the treatment of uncomplicated ADHD. They can, however, help the child or adolescent who has ADHD complicated by severely disruptive behavior. For example, a child with ADHD or ODD who is prone to outbursts of rage that are not controlled by other medications such as antidepressants or clonidine may require a mood stabilizer. 

Antidepressants and clonidine are the most commonly used augmentation strategies for ADHD. If the patient has tics or is troubled by insomnia, clonidine is a reasonable choice. After collecting a baseline EKG, clonidine should be started at 0.05 mg at bedtime for children and adolescents and 0.1 mg at bedtime for adults. The dose can be increased every 2 weeks or so while monitoring the patient s blood pressure and pulse. Although it has not been studied as well, guanfacine may work in much the same manner as clonidine. 

When stimulants cannot be used, clonidine or antidepressants are the best initial treatments for impulsivity. As noted earlier, more aggressive measures including antipsychotics and mood stabilizers may be needed in severe cases. 

Drugs that may interact with clonidine include beta-adrenergic blocking agents and tricyclic antidepressants. 

Drugs that may be affected by dexmethylphenidate or racemic methylphenidate include antihypertensive agents, pressor agents, coumarin anticoagulants, anticonvulsants, tricyclic antidepressants, selective serotonin reuptake inhibitors, and clonidine. 

Clonidine is an agonist at a - and o 2-adreno-ceptor subtypes. It reduce the sympathetic tonus and is thereby a useful antihypertensive drug. Clonidine can induce sedation, depression and peripheral side effects like a dry mouth. Unspecific a-adrenoceptor blocking agents like tricyclic antidepressants can reduce the antihypertensice effect of clonidine. 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

As noted above, Zito and colleagues (2000) reported stimulant use in a Medicaid population of 12.3/1000 preschoolers, with rates of stimulants, antidepressants, and other medications such as clonidine increasing dramatically since 1991. Unfortunately, in the absence of efficacy data and details on the actual diagnoses of the children, as well as no documentation of the children s actual functioning or types of care received, this study... 

Cervo L, Rossi C, Samanin R The role of serotonin and dopamine in brain in the antidepressant-like effect of clonidine in the forced swimming test. Neuropharmacology 31 331-335, 1992... 

A number of clinical trials have found clonidine to be superior to placebo in treating ADHD ( 101, 102,103 and 104). However, these studies were generally not as methodologically rigorous as those with either psychostimulants or antidepressants. Clonidine has been used as monodrug therapy and in combination with methylphenidate. Hunt (101) did a crossover study of clonidine alone, methylphenidate alone, and the combination in 25 children with ADHD and conduct disorder. 

The combination was reported to be superior to either agent alone in reducing parent ratings of conduct problems. However, the combination has never been tested in children with ADHD alone for the core symptoms of hyperactivity, inattention, and impulsivity. There is also concern about the safety of this combination because there have been four deaths in children (105). However, there were enough complicating factors present in each of these cases that no conclusions could be drawn about the role of methylphenidate and clonidine in these deaths. For these reasons, the use of clonidine for the treatment of ADHD should be tried only after trials of more than one psychostimulant and after an antidepressant trial. 

Tricyclic antidepressants potentiate the pressor effects of directly acting sympathomimetic amines, such as adrenaline (epinephrine) or noradrenaline (norepinephrine), to cause hypertension. Small amounts of these, such as may be present in local anaesthetic solutions, can be dangerous. Tricyclic antidepressants will inhibit the antihypertensive effects of the older anti hypertensive drugs, such as adrenergic neurone-blocking agents, e.g. guanethidine, a-methyl-DOPA, and clonidine. 

Many inhibitors of the amine transporters for norepinephrine, dopamine, and serotonin are used clinically. Although specificity is not absolute, some are highly selective for one of the transporters. Many antidepressants, particularly the older tricyclic antidepressants can inhibit norepinephrine and serotonin reuptake to different degrees. This may lead to orthostatic tachycardia as a side effect. Some antidepressants of this class, particularly imipramine, can induce orthostatic hypotension presumably by their clonidine-like effect or by blocking 04 receptors, but the mechanism remains unclear. 

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