ADHD Nonstimulants: Alpha-2-Adrenergic Agonists

00:01 Hi, I'm Doctor Rhonda Lawes and this is the discussion on the use of non stimulants in the treatment of ADHD.

00:08 Specifically we're going to look at alpha two adrenergic agonists.

00:12 Now the two examples we're going to use here are clonidine and guanfacine.

00:17 Okay. So we've got those two as example drugs.

00:19 But these medications since they're agonists they're going to stimulate the alpha two receptors. Now most predominantly the alpha two receptors that are in the prefrontal cortex. That's good news for those with ADHD because that will help with those executive functioning kind of skills.

00:35 So clonidine stimulates the alpha two A, the alpha two B and the alpha two C receptors.

00:41 Specifically Guanfacine selectively stimulates the alpha two receptors.

00:47 Now why does this matter to you? Well, you're going to have fewer side effects with guanfacine because it has a higher selectivity for the alpha two receptors.

00:56 You're going to have more side effects with the clonidine because it hits the alpha two A, two b, and the two c.

01:03 Let's look at the at the physiological effects by the receptors.

01:07 Now the presynaptic receptors are different than what you'll see in the postsynaptic receptors. But starting with the presynaptic receptors it's going to be primarily the alpha two subtype.

01:18 Now when you hit those alpha two receptors they're the main mediators of the effects of the norepinephrine.

01:24 Now this helps the client with inattention, hyperactivity and impulsivity.

01:29 So that's what they benefit from the activation of the Alpha two A's.

01:34 Now the alpha two receptors are particularly found in the cortex and the locus coeruleus.

01:40 Now let's look at the postsynaptic receptors alpha two A, B and C and also the alpha one subtypes of alpha one a, one b and one d.

01:52 So take away points from here.

01:54 There's different specific receptors in the presynaptic receptors and the postsynaptic receptors. And you've learned where we have the highest function of the two A's where it's located. And that they're the main mediators of Of norepinephrine.

02:08 So your clients are going to have a better opportunity to pay attention.

02:12 Deal with the hyperactivity symptoms and impulsivity.

02:15 Now the adverse effects of the alpha two is the most prominent ones are going to be the sedation. Remember you're going to have more side effects with clonidine than you will with guanfacine because guanfacine is more selective.

02:27 But the most prominent you're going to have sedation.

02:29 They may also have orthostatic hypotension.

02:32 So remind them about safety.

02:34 If they're jumping up quickly they're going to get a little dizzy.

02:37 It can also slow down the heart rate.

02:39 It can be bradycardia.

02:40 They may show some depression, some change in mood and they may complain of headache.

02:46 So these are the most prominent ones the ones you're most likely to see.

02:50 Now how do you know when you should use this or when you should absolutely not use the alpha two adrenergic agonist? Well, this is used for the treatment of ADHD in children who are at least six years of age. You can also use it with adolescents and with adults.

03:05 The people it is contraindicated to use this with are the following If the client is hypersensitive to any part of this type of medication, then you obviously wouldn't want to prescribe it. If the patient is cardiovascular or cerebral vascular disease, you would also want to be very cautious.

03:23 If you choose to give that.

03:24 This would require really thorough assessment to this patient.

03:28 Now last, if this client is on another alpha two agonist, you don't want to prescribe an additional alpha two agonist to treat the ADHD.

03:38 Now there are some additional indications or use cases for alpha two adrenergic agonists.

03:43 So usually think about reserving them for patients if they have any of the following situations. So if the patient has difficulty initiating sleep these are good drugs.

03:53 Remember they can cause that sleepiness.

03:55 If the client's had a poor response to a trial of a stimulant or an snri.

04:00 This might be a drug you'd want to consider prescribing.

04:02 Now, if the patient experienced unacceptable adverse effects with other medications, this is an option.

04:08 If the patient has a significant co-existing condition, they may want to want to choose an alpha two rather than a type of stimulant.

04:16 Now, if the patient has some other contraindication to stimulants, again, you would want to try an alpha two adrenergic agonist.

04:23 And finally, if the patient has tics or Tourette's, this would not be a good choice to give them a stimulant.

04:29 And so an alpha two adrenergic agonist might be applicable.

04:34 So keep in mind these can be used in ADHD.

04:37 But as a class they're not as effective as stimulants.

04:41 But they definitely have a place in your toolbox for clients who need to try an alternative. Now, when it comes to prescribing and termination, let's look at what you'll do as a provider.

04:51 You'll need to educate your patients that it could take up to two weeks for them to really experience a kind of response to this medication.

04:58 So make sure you set their expectations appropriately and let them know it's going to be a while before they may notice a difference.

05:04 Obviously, you're going to want to start at a low dose, typically at bedtime, because of the potential for sedation.

05:10 Now you're going to titrate to the desired effect.

05:13 And this will involve communication with your client.

05:16 This is not a medication that you'll need to take drug holidays.

05:19 They'll need to keep taking this every day.

05:22 Now, when it comes to discontinuing or terminating the script, make sure you try to avoid an abrupt discontinuation.

05:29 You want to taper this gradually.

05:31 You want to wean the medication so that you avoid significant rebound hypertension or nervousness. Now be aware that withdrawal symptoms you can treat them by up titrating the medication again and then tapering it.

05:44 But this time do it more gradually to avoid those withdrawal symptoms.

05:49 Now we created this study chart for you and this will help you compare clonidine and guanfacine. Remember those are two alpha adrenergic agonists that we're using as examples. So take a look at the chart.

06:00 Hey sometimes charts can be so helpful, but they don't really work unless you spend some time working with them.

06:06 So across the top let's get oriented.

06:09 The name of the medication.

06:10 So you see we have both clonidine and guanfacine.

06:13 We have the available formulations right.

06:16 And then you have the typical titration schedule.

06:19 Now for clonidine.

06:20 You can have either an oral tablet or a transdermal patch.

06:24 Now for the tablets. They come in immediate release or extended release.

06:28 But if you look at the typical titration schedule, you see they're exactly the same.

06:33 Both of these are nightly dosing.

06:35 You can titrate them every two weeks with a maximum dose of 0.4mg daily.

06:41 So those are the oral tablets.

06:43 Now clonidine also comes in the form of a transdermal patch.

06:47 Now this would typically not be your first choice to start someone on clonidine for ADHD. With a transdermal patch.

06:54 But it might be a good idea to convert them from the oral formation once you've got them on an optimal stable dose.

07:02 Now let's take a look at guanfacine.

07:03 Now you see it's an oral tablet.

07:05 Same thing. You have immediate release and extended release.

07:08 Now, with the immediate release, you're going to start with nightly dosing.

07:11 And then you can increase the frequency up to four times a day.

07:15 You start with a nightly dose to kind of let them adjust to that sedative effect.

07:19 And then you can gradually add the extra doses.

07:22 Now you can titrate every two weeks, so you don't want to make a change until they've had two weeks on that dosage.

07:28 And then you can start titrating it up.

07:30 Now, the maximum dose of four milligrams is what you use for children less than 12 years of age, and seven milligrams for adolescents and adults.

07:39 Now, with the extended release tablets, you can also up titrate those every two weeks.

07:44 Now, once daily dosing can be a max of four milligrams for children that are less than 12 years of age, and again, seven milligrams for adolescents or adults.

07:55 Now, while you have this chart, make sure you take a look at the things that are similar as we did when you and I were studying and walking through it together.

08:02 And the things that are different that will help you force that information into your longer term memory.

08:09 So you can recall it when you need it.

08:11 Now, I wanted to go over at the very bottom, look at extended release and immediate release. Tablets have different pharmacokinetic properties, so don't substitute them on a milligram per milligram basis.