According to the many well designed trials and reports, there is an important correlation between hypertension and psychiatric disorders. Psychiatric patients are often treated with antihypertensive agents. If we know that treatment with antidepressants and antipsychotics is often long-term we should be very careful, which antihypertensive agent is appropriate for these special patients. These patients are often treated with different specialists and many drug-drug interactions (e.g. indapamide-clozapine) occur within pharmacotherapy.
My opinion with the use of EBM:
- ACE inhibitors should be used first and those with longer half life (especially those with appropriate pharmacokinetics accroding to the kidney failure; e.g. Fosinoprilat). Because psychiatric patients are usually treated with antidepressants (e.g. trazodone) and antipsychotics (e.g. clozapine and quetiapine), which can make hypotension it is very important to use ACE inhibitors with longer half life (to avoid serious short hypotension and falls).
- diuretics (e.g. Indapamide) should be avoided. Although these agents are second line in many international guidelines for hypertension treatment they can incude serious prolongation of QTc, which can have very bad consequences (e.g. death, torsade). We know that many psychiatric patients are treated with those drugs and we can expect additional action, when many 'dangerous' drugs are used together (e.g. TCA, clozapine, quetiapine, amisulpride etc ... ). Instead of diuretics use CA-antagonist for example (e.g. amlodipine, because is cheap and effective).
- sartans are second line treatment (ACE inhibitors first line). However valsartan could be a good idea in patients where Fosinoprilat is not effective and we have psychiatric patients with kidney failure.
- beta-blockers are very useful in these patients, especially where we can avoid polypharmacy (e.g. propranolol for tremor and hypertension) and add additional efficacy (e.g. pindolol in depression and hypertension). However use of these drug should be with great caution especially in the elderly psychiatric patients.
Especially a great caution is required, when used these drugs in patients with ADHD. In these patients avoid of the use of beta blockers because serious hypertension can occur, especially when withdrawal is taking place.
- Moxonidine could be a good option in some patients, however drug drug interactions can be very dangerous. To add moxonidine to ACE inhibitors and CA-antagonists could be a better option as add diuretic indapamide.
- Alpfa blockers are not first line treatment, especially in elderly psychiatric patients. Many DDIs can be very dangerous (e.g. pharmacodynamic) and serious hypotension can occur, when used together with antidepressants and antipsychotics.
If i sum up, it is very important to check all possible DDIs before prescribing. It is also very common that psychiatric agents with its mechanism of action have potential to lower blood pressure and usually in these patients antihypertensive agents can be reduced. However, a cooperation among clinical pharmacists and clinicians can be beneficial for these patients.
YES ,Your research is highlighted on effect of antihypertensive drug on psycatric disorder or condition ,above mentioned all drugs might produce toxicity on nervous system ,but according to research Methyldopa is one of the best drug with negligible toxicity use in hypertensive condition.
Thank you
Dr./Prof. Stuhec,
You have performed a very nice review of anti-hypertensive classes. The flaw that I perceive in your question is that in clinical medicine we treat individual patients and not lump all psychiatric patients into one class. I can't begin to believe that all psychiatric patients are the same. Labeling a patient as "psychiatric" does not impart a constellation of comorbid conditions or polypharmacy. Be careful with making clinical assumptions
What I will share: in over 20 years of treating patients with or without behavioral issues, I never recommended METHYLDOPA. We euphomistically refer to ALDOMET as "I'll make you doppy". It causes drowsiness and interferes with cognitive function. It is a dangerous drug in an archaic class of anti-hypertensives
Good luck,
Dr Gerry Lane
Dear Dr Gerry Lane,
thanks for this opinion. I agree with You. I also do not suggest METHYLDOPA to these patients (maybe only to pregnant patients!). I usually want to suggest drug which do not pass blood-brain barrier, which is seen in the most of ACE-inhibitors. However in some cases beta-blockers (lipophilic) are fine option, especially when OCD, tremor and anxiety are under question. Pindolol is also useful in these patients, when we want additive efficacy and 5HT1a activity.
METHYLDOPA and alpfa-1 blockers can be problematic in these patients, because many additive effects are possible (especially with stimulants and antidepressants). There are large possibility for DDIs, especially the pharmacodynamic ones with these drugs. I would suggest to avoid METHYLDOPA in the patients, except pregnant patients with psychiatric disorder without stimulants and antidepressants with common target receptors (e.g. reboxetine, duloxetine, venlafaxine).
What i see as clinical pharmacist specialist within psychiatry is widely use of older beta-blockers (e.g. atenolol), which are not very effective nor safety. Especially in these patients, who are often treated with antipsychotics (e.g. quetiapine) and antidepressants (e.g. trazodone) a hypotension is seen very often, which can be especially problematic in the elderly patients. If carvedilol and metoprolol are used I suggest their use by food (hypotension is less problematic). The second important issue, which i see is necessity of drug regimen adjustment after treatment with antipsychotics (e.g. quetiapine), because of down regulation of receptors and hypertension is often see after 2-4 weeks of the treatment with quetiapine.
Regards,
Dr Matej Stuhec
Although, it is a very old drug but reserpine can be used as it will also calm down the aggression that can be seen openly or hidden in patients with psychiatric diseases. However caution is required to be used in patients with depressive illness.
I am against of the use of reserpine, because it has many of very important side effects. I would be rather stay with ACE-inhibitors. Calcium antagonists can be also problematic, because many DDIs are possible, especially with amlodipine and carbamazepine and quetiapine.Reserpine is also not available in many countries..
In the case of comorbidity between depressive Disorder and hypertension I choose in most of the cases antidepressant: amytriptilin (old drug) - if there are no risk factors . (heard disorders), because of its anti depressive and antihypertensive action. My experience shows that it is possible just with this, one drug to treat the depressive symptoms and in the same time to control blood pressure. At the first 2 weeks is gut 1/day the patient to measure the blood pressure - in the case the blood pressure starts to drop I recommend reduction and stop of the hypertensive drug. The patients are very satisfied because 1. the psychiatric symptoms are reduced or gone and in the same time 2. they do not need antihypertensive drug. I have not jet seen from the novel antidepressants to have this dual function. Side effects by slow increase of the dosage are very very selten.
Regards
Dear Aleksandra,
as clinical pharmacist specialist within psychiatry i often deal with these patients.
After i have reviewed your comment I have several concerns about the 'routine' use of amitriptyline for these purposes:
1) Amitriptyline is very old drug, which is not first line treatment for depressive disorder or similar problems (OCD, GAD etc ... ).
2) Amitriptyline has serious adverse effects, especially anticholinergic adverse effects are very frequentl (according to the epidemiological data app. 30-50 % patients). Anticholinergic adverse effects are very dangerous in elderly psychiatric patients, because cognitive functions are depressed and obstipation is very often seen. On almost all lists with inappropriate prescribing in the elderly patient amitriptyline is updated (Priscus, STOP/START ...).
3) Amitriptyline is problematic in the case of cardiovascular disorders (prolongation of QT, arrhythmias) and If cardiovascular patients are treated with thia agent serious adverse events are possible. We know that comorbidity between depression and CHF is high.
4) We know that depressed patients are more often treated with several additional agents, for example antibiotics. And many of these combinations are even almost contraindicated (e.g. ciprofloxacin) and important DDIs can occur in these patients.
5) Amitriptyline is problematic in the case of several DDis, which is especially concern in the elderly psychiatric patients, which are often treated with polypharmacy. Additional pharmacodynamic interactions, especially anticholinergic ones, are very problematic and can lead to serious harms. Chronic obstipation is seen often and cognitive damages. For example: patient is already treated with carbamazepine, valproic acid/valproate and solifenacin. If You add amitriptyline the probability for serious adverse event is even tripled.
6) Amitriptyline is problematic in the case of patients with dementia. Because of its mode od actions this agent can lead to serious harms and additive cognitive decline. Interactions between drugs for dementia treatment and Amitriptyline are also possible and therefore treatment discontinuation with Amitriptyline is necessary.
7) Amitriptyline and its toxic potential. This is one of the most dangerous agents in this field with very narrow therapeutic agent and many deaths are consequences of high doses of Amitriptyline for which is usually TDM not possible, although it is necessary.
What to use in these patients?
1) ONLY TRAZODONE
If we have these patients We can try with trazodone, which is safer than Amitriptyline and many positive trials in the elderly patients are known, although QT monitoring is obligatory for these patients.
2) TRIAL with ANTIHYPERTENSIVE DRUG (ACE)
After remission is established there is often place to discontinue with antihypertensive agent.
3) TRIAL WITH QUETIAPINE
In several patients the 'off label' use of quetiapine has positive additional effect. In addition We have some trials an indication in several countries for MDD additional treatment. After remission is established drug discontinuation is possible if serious hypotension is measured.
If I add the important topic:'down and upregulation of receptors'. Usually a hypotension is established with alpha-1 adrenergic activity of several agents (e.g. quetiapine, Amitriptyline and trazodone). This activity is less active after several weeks because of mRNA activity and down regulation of receptors. Consequence of this action is high blood pressure and therefore a great caution is advisable when prescribe these agents to psychiatric patients with hypertension.
Best regards from Slovenia to Austria,
Matej
There are two points in this question. (1) Use of single drug which treats psychosis and hypertension; perhaps none exists except reserpine-a baby who is not fed because it is not crying!. We may avoid reserpine, diuretics and propranolol in depression . The second part is concurrent use of antipsychotics/antidepressants with antihypertensives. . Generally if a drug does not share same metabolic pathway for inactivation, then DDIs would be less. Nevertheless, those drugs which enter BBB, would also produce some unwanted pharmacodynamic effects, which may be detrimental to a psychiatric case. Therefore, individualization of drug therapy shold be done, depending on the concurrent psychiatric disorder(Psychosis or depression) o and concurrent medications. Lisinopril for example is not all metabolised so is least likely to interact. CNS effects are negligible.
Dear Matej
Thank you for sharing your extensive knowledge and indeed experience in this complicated topic.
As for treatment of hypertension, HIV, cautious combination (yes I avoid the term polypharmacy) therapy has important role in effective treatment of individuals with psychiatric disorders.
Given the risk of DDIs, its important to have access to all the relevant information.
I use an app (for smart phone) called Epocrates.
Happy to learn about any other useful apps colleagues use.
Rashid
Dear Rashid,
I am glad to hear your news. I am totally agree with you that this is important topic, which is rarely under investigation, although is very important for our patients. As clinical pharmacist consultant within psychiatry usually suggest to make corrections in these pharmacotherapy. Especially antihypertension therapy is very important in elderly patients, who are often treated because of hypertension (more than 30 % of patients). According to the epidemiological data they are often treated with antihypertensive 'polypharmacy'. In many situations patients are not treated with desired outcomes (cmax-cmin differences) and hypotension often has been occurred. After psychopharmaceuticals are prescribed there are so called up and down regulation of receptors, which is seen often. After immediate hypotension, which is seen often with use of quetiapine, olanzapine, trazodone for example, hypertension occur after if many drugs are discontinued. After this important topic we should calculate about DDIs, although it should be used with great caution. Because 'real' DDIs are much more important than potential ones and there is big help if we use the knowledge of clinical pharmacology and especially epidemiological data from Medline (described cases and trials and case series). In my point of view a cooperation between clinical pharmacist within psychiatry and psychiatrists is beneficial for our patients. The most important is to reach our treatment goals, although teamwork is not often easy.
If I add an answer to one of the previous comment: I am against to use very old antihypertensive agent (e.g. plant drugs, old beta blockers) and one of the ACE-inhibitors is preferable in these cases with its inability to pass BBB.
Regards,
Matej
I prefer a combination of amlodipin+Sartan (olmesartan or valsartan) and a newer beta blocker like bisoprolol or nebivolol. Only two tablets but protection for heart , brain & kidney. Long acting hence less BP fluctuations. Counteracting each others potential side effects and adding synergistic action. Avoid directics because irregular food intake and potentiation of hypotensive effects and electrolyte imbalance may lead to vertigo and even fall as well as potential life threatening arrhythmias. Prof. Wadud
Dear Abdul,
the situation is not so easy as you described. Please keep in mind that almost 3-5 % (or even more) of patients with mood disorders and seizures are treated with carbamazepine, which has clinically important interaction (DDI) with amlodipine. If You use amlodipine and carbamazepine is introduced there is big risk of therapeutic fail (hypertension will occour). Oxcarbazepine has fewer potential toward this DDI and also quetiapine. In these cases i suggest not to use amlodipine in patients with mood disorders and seizures. One of possible therapeutic alternatives is abolutely lacidipine, which is more expensive, however more suitable in these cases (to avoid this important DDIs).
In these patients an additional agent, which has an impact on 3A4 and especially 2D6 and 1A2 metabolic pathway can lead to several DDIs and because of that reason it is highly advisable to avoid use of these agents.
In addition, there is a great evidence that use of ACE-inhibitors is the most appropriate treatment strategy in these patients. I do not agree with Abdul that sartanes should be used. Why? Sartanes are more expensive and we have more evidence about the use of ACE inhibitors for many indications. Please keep in mind that there are more possible that DDIs will occur. Metabolism of losartan for example is primarily by cytochrome P450 isoenzymes CYP2C9 and CYP3A, which is not very appropriate in several cases. More than 5-7% of these patients are treated with quetiapine and several important DDIs can occur. About 14% of an oral dosage is converted to this metabolite, which is long-acting (6 to 8 hr) and a noncompetitive antagonist at the AT1 receptor, contributing to the pharmacological effects of losartan. EXP3174 is 10-40 times more potent in blocking AT1 receptors than losartan ... If you use quetiapine in high doses, for example 500-800 mg daily for bipolar disorder or SCH there is high risk of serious hypotension, because titration of quetiapine is very fast (50-100 mg daily).
If i conclude, there is very hard to say easy answers for these complicated topic. However, more than 20 % of patients with mood disorders and seizures are treated with antihypertensive agents and this topic becomes more important for clinicians, clinical pharmacists and our patients.
I would suggest to use ramipril (It has also low possibility to pass BBB.and low ability for DDIs no CYP metabolism), except in patients who are treated with lithium. In these patients i would suggest to use lacidipine.
Regards,
Matej
combination of cilinidipine and telmesartan can also be agood alternative
i do not have any good reason why to use sartan instead of ACE-inhibitors in these patients. Maybe only these where prodrug is included. If we know that ACE inhibitors are used more often and have more approved indications, for example ramipril and enalapril.
I normally use ACE inhibitors
Sometimes ACE inhibitors associates a diuretics
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