Symptomatic treatments

Let’s look at treatments for Alzheimer’s disease. We have symptomatic treatment on the one hand and pathophysiological treatment on the other. To clearly explain the difference between the two, let’s take toothache as an example. When your tooth hurts, you have two options. 

You can treat the symptom – that is, the pain – and take an analgesic such as paracetamol. This is symptomatic treatment. You haven’t treated the cause but the symptom – or the consequence. Option number two. You go to the dentist, who will either treat the cavity or extract the tooth. This is a radical form of treatment, or what we call pathophysiological treatment. Let’s look at symptomatic treatment in Alzheimer’s disease, which includes treatments for cognitive and psychobehavioural symptoms. 

First, as regards cognitive symptoms, some drugs developed to treat Alzheimer’s disease were found to improve cognitive disorders, as shown in a number of well-conducted double-blind studies. You can see here, for example in blue, the effect of the treatment on patients with cognitive symptoms over six months, up to the green box. At the bottom in grey, you can see the progression of patients who were not treated. 

Compared with non-treated patients whose cognitive symptoms deteriorated, treated patients (in blue) remained above their baseline performance and continued to improve. The green box depicts the moment when treatment is stopped, which is called the ‘washout’ period. When this happens, the patients join those who were not treated, which confirms that the treatment is symptomatic – the cognitive symptoms are treated. A number of well-conducted studies have shown these drugs to be effective, but their efficacy is moderate. 

The French Health Ministry decided that these drugs would not be reimbursed, and they no longer are. French neurologists disagree with the decision because the drugs do work. Their efficacy, though moderate, has been proven. When we stopped using the drugs because they were no longer reimbursed, we found that the patients’ conditions deteriorated. It’s a shame, but that’s how it is. Now, all treatment – whether symptomatic or psychobehavioural – is offered when patients are agitated or irritable or when they display delusional behaviour. 

We should therefore pay close attention to these drugs, which can be helpful. But we must also be careful and make sure that the behavioural disorder is not due to a somatic cause, as discussed when we covered behavioural disorders. We should also try to combine medicines, which could be aggressive for brains weakened by Alzheimer’s, with other methods such as the non-drug techniques already mentioned. 

There are four main categories of drugs that can be prescribed to patients with psychobehavioural disorders. The four categories are neuroleptics, antidepressants, benzodiazepines and hypnotics. We will discuss them one by one. Should neuroleptics be proscribed? To prescribe or to proscribe – that is the question. Prescribing a neuroleptic to patients with major neurocognitive disorders will cause the illness to progress. Unfortunately, these drugs have side effects that will make the patient’s condition deteriorate. 

That’s why we must be extremely mindful when prescribing neuroleptics. By doing so, we expose the patient to extrapyramidal symptoms and parkinsonian syndromes. You often see elderly patients with Alzheimer’s who have a slight tremor… Often, it’s because they are treated with a neuroleptic. They are at risk of delayed dyskinesia, falls, and fractures linked to orthostatic hypotension, which can lead to dizziness or fainting combined with falls. They can also experience heart rhythm disorders and are at risk of stroke or even death. Such drugs must therefore be prescribed with a great deal of caution. That said, it’s true that when patients are agitated or extremely irritable, when all other causes have been ruled out and we cannot reduce the agitation, a neuroleptic drug – if administered correctly at the right dosage – can be a suitable solution. 

Remember that for patients with a history of delirium, neuroleptic drugs can be used in the case of behavioural disorders with an underlying chronic mental illness. Neuroleptic drugs can be extremely useful. If a delusional process is involved, we should not hesitate to prescribe neuroleptics. It’s important to remember that the drugs are ultimately not all that effective. You can see it on the curve compared with the placebo in yellow. The drugs have a certain efficacy, but it’s not all that different from a placebo. 

On the other hand, neuroleptics involve side effects and a significant intolerance. As already mentioned, we must be careful when prescribing them. Moving on to benzodiazepines… I will share some key points. One of the main indications is acute anxiety. Another is insomnia, although then the treatment is short-term. Benzodiazepines can also help with agitation, aggressivity and irritability. 

When using neuroleptics, choose drugs with a short half-life because elderly patients often have mild kidney failure, which creates a risk that the benzodiazepine will have a longer half-life. If possible, do not combine two benzodiazepines or a benzodiazepine and a hypnotic. 

There is no reason to combine two benzodiazepines. Be cautious when combining benzodiazepines with a neuroleptic. Note that these drugs involve a risk of daytime drowsiness and falls because they cause mild confusion. Lastly, as regards antidepressants, many are relatively well tolerated – such as selective serotonin reuptake inhibitors (SSRIs) and noradrenaline reuptake inhibitors (NRIs). 

They have a good safety profile in Alzheimer’s disease, and little to no anticholinergic effect, so they are often used as first-line treatment. In our experience their efficacy has been moderate, but they are a suitable option in all forms of depression. If antidepressants can’t be avoided, it’s best to use SSRIs or NRIs.