This is part of a psych meds 101 series written from my perspective as mental health nurse, ex-pharmacist, and psych med users. Previous posts have covered antidepressants, antipsychotics, and mood stabilizers, and an upcoming post will touch on sleep meds. Much of this post will focus on the benzodiazepine class of medications, but I’ll also cover other meds used for anxiety.
Benzos bind to GABA-A receptors on neurons to boost the activity of the neurotransmitter GABA, which exerts a calming effect on the brain. GABA counteracts the excitatory neurotransmitter glutamate. Besides being used for anxiety, benzos are used for acute management of seizures and alcohol withdrawal. Very rapid- and short-acting benzos like midazolam may be used for procedural sedation. Despite their downsides, benzodiazepines (benzos for short) work for anxiety. They work very well, and they work quickly. And that’s what makes them so darn problematic.
Duration of action
Drugs within the benzodiazepine class differ considerably in their half-lives, i.e. the time it takes for the body to clear half of the medication. Half-lives are also affected by a given individual’s ability to metabolize the drug. The half-life of lorazepam (aka Ativan) can range from 8-24 hours, and clonazepam’s half-life is 19-60 hours. Time of onset tends to be between 20-60 minutes after administration.
Taking benzos regularly for an extended period will lead to tolerance. Full stop. How long it takes and the extent to which it happens may vary from person to person, but over time the same benzo dose will produce less of a therapeutic effect. A general rule of thumb is that benzos work best the less you take them. Ideally, this might look like finding another medication for sustained use and using a benzo as needed (prn) for breakthrough anxiety symptoms. Of course, we don’t live in an ideal world and for some people benzos are the only thing that helps them get through the days. Still, it’s the kind of thing you want to know about going in rather than finding out after you’ve already been on regular benzos for a year.
That brings me to my next point: withdrawal. Withdrawal can range from nasty (increased heart rate and blood pressure, cramps, anxiety, insomnia, impaired memory and consciousness) to downright dangerous (high fever, seizures, psychosis). Withdrawal results from physiological dependence, where essentially your body chemistry changes to adapt to the regular presence of the drug. We might think of addiction as involving both a physiological and a psychological dependence, but whether you consider yourself addicted or not if you have been on long-term high-dose benzos and you stop cold turkey, you will have withdrawal. Getting off of benzos requires a gradual tapering down of the dose, and even then it can be a really tough experience. That brings me back to my earlier point; it’s good to know going in that benzos work best the less you use them, if that’s something that’s feasible for you.
Antidepressants that promote serotonin neurotransmission can help to settle down the amygdala, part of the primitive caveman brain that is associated with anxiety, fear, and panic. SSRIs (selective serotonin reuptake inhibitors) or SNRIs (serotonin and norepinephrine reuptake inhibitors) are commonly used. Older antidepressants from the TCA (tricyclic antidepressant) or MAOI (monoamine oxidase inhibitor) classes may also be used and are quite effective, but they are more likely to cause side effects. Typically higher doses are required than for the treatment of depression, and it can take longer to see a therapeutic effect because of the complex signalling loops that are involved. In OCD, it can take up to 10 weeks for SSRIs to be effective. It can be a frustrating waiting game, and benzos can certainly be useful in getting through this.
This acts on 5HT1a serotonin receptors to suppress neuron firing in a portion of the brainstem known as the dorsal raphe nucleus. It may take a few weeks to become effective. It’s an older drug that’s not used all that commonly, but a psychiatrist that I used to work with often prescribed it and found it to be quite effective without a lot of side effects. It’s not addictive and not sedating, so it’s a pretty low-risk medication to try out.
These anti-seizure medications act on the transporter that moves calcium ions in and out of neurons. This helps control the release of the excitatory neurotransmitter glutamate in the amygdala. While these are not among the anti-seizure medications that have demonstrated mood stabilizing activity, they can be useful for anxiety. They’re not addictive, although some people experience discontinuation symptoms if they’re taken off too quickly. Both gabapentin and pregabalin are dosed three times a day. Gabapentin has a wide dosing range, so it may take some tweaking to get the right dose.
Atypical antipsychotics may also be useful. It’s not entirely clear how they exert this effect, but it may be related to changes in norepinephrine and serotonin signalling via interaction with alpha-2 adrenergic receptors. Quetiapine is commonly used for anxiety, and risperidone has demonstrated effectiveness in obsessive compulsive disorder. Atypicals may be used as an add-on treatment for longer-term management or for prn (as needed) use. Generally lower doses are required than for management of psychosis.
Clonidine acts on alpha-2 adrenergic receptors. While it has shown some effectiveness, this doesn’t tend to be sustained, and it’s not considered a first-line treatment option.
Beta blockers like propranolol can settle down some of the body’s fight-or-flight response, and can be useful for “performance anxiety”. It tends to target the physical effects of anxiety rather than the mental experience.
This isn’t an exhaustive list by any means. There are some other medications including mood stabilizers that may be used, and treatment of choice varies depending on the particular diagnosis. In the recent DSM-5 PTSD has been moved out of the anxiety disorders category, so I haven’t touched on that at all here.
Next up in the psych meds 101 series will be sleep meds zzzzz……