Stimulants Bupropion

Isolated seizures that are not epilepsy can be caused by stroke, central nervous system trauma, central nervous system infections, metabolic disturbances (e.g., hyponatremia and hypoglycemia), and hypoxia. If these underlying causes of seizures are not corrected, they may lead to the development of recurrent seizures I or epilepsy. Medications can also cause seizures. Some drugs that are commonly associated with seizures include tramadol, bupropion, theophylline, some antidepressants, some antipsy-chotics, amphetamines, cocaine, imipenem, lithium, excessive doses of penicillins or cephalosporins, and sympathomimetics or stimulants. 

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. 

The tricyclic antidepressants (TCAs), such as imipramine, can alleviate symptoms of ADHD. Like bupropion, TCAs likely will improve symptoms associated with comorbid anxiety and depression. The mechanism of action of TCAs is in blocking norepinephrine transporters, thus increasing norepinephrine concentrations in the synapse the increase in norepinephrine is believed to alleviate the symptoms of ADHD. TCAs have been demonstrated to be an effective non-stimulant option for ADHD but less effective than stimulants. However, their use in ADHD has declined owing to case reports of sudden death and anticholinergic side effects6,13 (Table 39-3). Further, TCAs may lower seizure threshold and increase the risk of car-diotoxicity, (e.g., arrythmias). Patients starting on TCAs should have a baseline and routine electrocardiograms. 

Many neurotransmitters are inactivated by a combination of enzymic and non-enzymic methods. The monoamines - dopamine, noradrenaline and serotonin (5-HT) - are actively transported back from the synaptic cleft into the cytoplasm of the presynaptic neuron. This process utilises specialised proteins called transporters, or carriers. The monoamine binds to the transporter and is then carried across the plasma membrane it is thus transported back into the cellular cytoplasm. A number of psychotropic drugs selectively or non-selectively inhibit this reuptake process. They compete with the monoamines for the available binding sites on the transporter, so slowing the removal of the neurotransmitter from the synaptic cleft. The overall result is prolonged stimulation of the receptor. The tricyclic antidepressant imipramine inhibits the transport of both noradrenaline and 5-HT. While the selective noradrenaline reuptake inhibitor reboxetine and the selective serotonin reuptake inhibitor fluoxetine block the noradrenaline transporter (NAT) and serotonin transporter (SERT), respectively. Cocaine non-selectively blocks both the NAT and dopamine transporter (DAT) whereas the smoking cessation facilitator and antidepressant bupropion is a more selective DAT inhibitor. 

Dopamine-Stimulating Medications. A variety of drugs that increase the availability of dopamine have been studied in cocaine addicts including L-DOPA, bupropion, amantadine, and methylphenidate. In small uncontrolled trials, these have shown some benefit, but definitive studies have yet to be performed. In addition, some dopamine-stimulating medications (in particular, the stimulants like methylphenidate or the amphetamines) are themselves subject to abuse, though, of note, this is typically not a problem when they are prescribed to patients who do not have a history of substance abuse such as, for example, in the treatment of attention deficit-hyperactivity disorder. 

Bupropion (Wellbutrin, Zyban). Bupropion is a newer atypical antidepressant that was initially suggested to increase both norepinephrine and dopamine activity in the brain, though controversy surrounds this hypothesis. Although bupropion has not been studied extensively in ADHD, early evidence does indeed indicate that it may be effective for both inattention and hyperactivity/impulsivity. Its effectiveness for ADHD does not appear to rival the stimulant medications, though a recent controlled study for adult ADHD showed that bupropiou outperformed placebo. 

If depression is a problem, many clinicians prefer an antidepressant as an augmentation strategy. Because of the problems mentioned earlier, most now avoid using TCAs to treat ADHD. Bupropion, SSRIs, and venlafaxine are viable alternatives, and may add to the effect of the stimulant. Bupropion and venlafaxine are believed to offer some additional improvement in attention. SSRIs may be more likely to improve impulsivity. Each should be started at a low dose and increased gradually. None of these are approved for use in children however. 

There are four classes of antidepressants tricyclic antidepressants (imipramine, trimipramine, amitriptyline, doxepin, desipramine, protriptyline, nortriptyline, amoxapine, maprotiline) monoaminooxidase (MAO) inhibitors (phenelzine, isocarboxazid, tranylcypromine) second-generation antidepressants or atypical antidepressants, which are a chemically dissimilar group of recently proposed drugs (bupropion, trazodone, fluoxetine) and amphetamines and other stimulators of the CNS (dextroamphetamine, methylphenidate). 

Inattentiveness, impulsivity, hyperactivity 50% will continue to manifest the disorder into adulthood Stimulants (70% response for uncomplicated ADHD caution in patients with tic disorders) TCAs (70% response, first line for patients with comorbid MD or anxiety disorders, and for patients with ADHD + tics) requires serum levels and cardiovascular monitoring Bupropion Clonidine, guan-facine (first line for patients with ADHD + tics) MAOIs Combined pharmacotherapy for treatment-resistant cases... 

Case reports have suggested that adding stimulant medications or combining a SSRI and a TCA or bupropion may also be effective (APA, 2000), but these combinations need to be done with caution, given the possibility of drug interactions (e.g., SSRIs cytochrome inhibition leading to toxic TCA levels). Additionally, in adults, the combination of antidepressants and psychotherapy (CBT, IPT) for patients with severe or treatment-resistant depression has been found useful (APA, 2000 Keller et al., 2000). 

Hughes et ah, 1999 Plizka, 2000). This strategy has not been validated, however. Recently an open study using bupropion suggested that this medication can be efficacious to treat both MDD and ADHD (Daviss et ah, 2001), although its effect on ADHD is not as impressive as that obtained with stimulants (Conners et ah, 1996). 

Other alternatives to the stimulants that have been studied for treatment of ADHD in children and adults include the tricyclic antidepressants desipramine and nortriptyline the newer antidepressants bupropion, venlafaxine, and atomoxetine the beta-blocker pindolol and the selective monoamine oxidase inhibitor, deprenyl. Across these agents, the number of controlled studies varies from none (nortriptyline) to four (bupropion). Only deprenyl and desipramine have been studied in children with ADHD and tic disorders. 

Although more stimulating antidepressants (e.g., bupropion, SSRIs, venlafaxine, or certain MAOIs) do not potentiate alcohol, they can produce insomnia. To minimize this problem, the dose may be given earlier in the day. TCAs may cause episodes of excitement (rare), confusion, or mania, usually in patients with an underlying psychotic illness, suggesting that a preexisting disorder must be present for these drugs to exert any psychotomimetic effects. 

A number of antidepressants do not fit neatly into the other classes. Among these are bupropion,mirtazapine, amoxapine, and maprotiline (Figure 30-5). Bupropion has a unicyclic aminoketone structure. Its unique structure results in a different side-effect profile than most antidepressants (described below). Bupropion somewhat resembles amphetamine in chemical structure and like the stimulant, has central nervous system (CNS) activating properties. 

FIGURE 7—41. Adrenergic combo 2 Bupropion can be combined with a stimulant such as d-amphetamine or methylphenidate. The stimulant will add a double dopamine boost to bupropion, which boosts dopamine in its own right. A single boost of norepinephrine from bupropion also is present. 

Mood stabilizers and atypical antipsychotics may be helpful in patients who fail to have adequate responses to stimulants, alpha 2 adrenergic agonists, or bupropion,... 

Bupropion is free of anticholinergic, antiadrenergic, and cardiotoxic properties. Its structure is related to that of amphetamine and it possesses stimulating effects hence it may be useful in hyperphagic or obese individuals. 

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