Psych meds 101: Sleep meds

pills beside a glass of water

This is the last in the psych meds 101 series; I’ve previously posted about antidepressants, antipsychotics, mood stabilizers, and anti-anxiety meds, drawing on my perspective as a mental health nurse, former pharmacist, and person with depression.

While some of these meds are used  primarily for sleep, many have other uses as well.  The choice of medication for any given person will be based on their diagnosis among other factors, and sleep aids may no longer be necessary once the underlying mental illness is well controlled.

Benzodiazepines

I covered these in more detail in my previous post on anti-anxiety meds.  The choice of benzo will depend on whether you want it more for getting to sleep or staying asleep (i.e. shorter or longer acting).  I’ve found clonazepam, which is long-acting, to be helpful in the past when I was having problems with waking up early.

Oxazepam and temazepam do not have the same degree of anti-anxiety effect as other benzos, but they are useful for sleep because their half-lives match up pretty well with a night of sleep.  They are also are cleanly metabolized, meaning they don’t leave any active metabolites sticking around that can cause a hangover-type effect.  The key thing to be aware of when using benzos for sleep is that if you use them regularly you will develop a tolerance and they’ll become less effective.

Z-drugs

The so-called Z-drugs include zopiclone and zolpidem.  Their main therapeutic use is for sleep.  Like benzos, they act on GABA receptors (GABA is a calming neurotransmitter), but they act at a different site and cause different changes in the receptor.  As a result, they are less likely to result in dependence, tolerance, or withdrawal symptoms.  I’ve had moderate success taking zopiclone in the past, but I’ve needed 15mg rather than the most common dose of 7.5mg.

Anti-histamines

Histamine does a number of things in the body, but in the brain it promotes wakefulness.  Blocking H1 histamine receptors results in a sedative effect.  Most over-the-counter sleep medications include diphenhydramine, which is the drug found in Benadryl to treat allergies.  A downside of H-1 histamine blockers is that they can cause weight gain when used long-term.

A lot of the prescription medications that may be used for sleep block H1 receptors in addition to whatever their primary therapeutic purpose might be.  Trazodone is an antidepressant that’s used more often for sleep than as an antidepressant.  It’s used for sleep generally at doses of 50-150mg, and needs to be taken at higher doses for an antidepressant effect.  Tricyclic antidepressants like amitriptyline are quite sedating, as is mirtazapine.  Interestingly enough, mirtazapine is most sedating at lower doses, and at higher doses becomes more activating.  For me the sweet spot seems to be at 30mg.  Antipsychotics that affect H1 receptors may also be used for sleep, such as methotrimeprazine and quetiapine.  Quetiapine extended release can be useful if early morning awakening is a problem.

Anticonvulsants

Gabapentin is an option but not necessarily the most effective one.  It would tend to be most appropriate for someone who would also benefit from its other therapeutic effects, e.g. for neuropathic pain or anxiety.

Prazosin

Prazosin isn’t a sleep medication per se; however, for people with PTSD it can help tone down nightmares and thus improve sleep.  It blocks alpha-1 adrenergic receptors, slowing down some of the sympathetic nervous system fight-or-flight-related activity.

Melatonin

Melatonin is a hormone that is naturally produced by the pineal gland in the brain, and it’s involved in regulating the Circadian rhythm, i.e. sleep-wake cycle.  For some people melatonin supplements work well, such as people whose circadian rhythm gets disrupted by things like shift work.  For other people, taking melatonin doesn’t do much of anything; I happen to fall into this category.  Ramelteon is a drug that stimulates the same receptors as melatonin does, but I’ve never actually seen it used; melatonin is cheaper and more readily available.

Valerian root

This is a herbal product that may have some sort of activity at GABA receptors, although it’s not clear what exactly this is.  There isn’t a lot of evidence to back up its effectiveness, but it’s worth being aware of as a non-drug option.  I’ve tried it and personally didn’t find it helpful.

 

There are a variety of other non-drug options that are worth giving consideration to.  Tryptophan is an amino acid that is a precursor for serotonin production.  It’s the substance in turkey that’s associated with drowsiness, and can be taken as a supplement to promote sleep.  Herbal teas, particularly those containing chamomile, may be helpful.  There are also certain substances that it may be be best to avoid; caffeine is an obvious one, but perhaps not so obvious is alcohol.  Alcohol may help you get to sleep, but it decreases sleep quality and makes it more likely you will wake up during the night.  Sleep hygiene is very important, but I’ll address that in another post.

While ideally we wouldn’t need to take drugs to help us sleep, the reality of mental illness is that most of us will have problems with sleep at one time or another.  Given how hugely damaging poor sleep is to mental health, I’ll take drugs over insomnia hands down.  As with any kind of medications, knowledge is power, and knowing our options puts us in a position to make the best decision in our own specific circumstances.

 

Photo credit: pina messina on Unsplash

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Book review: Birth of a new Brain – Healing from Postpartum Bipolar Disorder

Birth of a New Brain book cover

Birth of a New Brain – Healing from Postpartum Bipolar Disorder chronicles author Dyane Harwood’s journey with postpartum onset bipolar disorder.  The story’s rich, vivid descriptions draw the reader along on the intense roller coaster ride of the author’s illness experience.  Many elements of her story will be hauntingly familiar to those whose lives have been touched in some way by bipolar disorder, including mood symptoms whose true nature only became apparent with hindsight and well-meaning attempts to get off medication that result in disaster.

Mental illness was a part of Dyane’s life from the beginning, as her father had bipolar disorder.  When she first began to struggle with her own mental health, she was diagnosed with depression.  Glimmers of hypomania made occasional brief appearances, but as is so often the case with hypomania the symptoms were only recognizable as such upon later reflection.

Depression is the most recognized postpartum mental health problem, while postpartum hypomania may not raise red flags.  As Dyane began to recognize that her thoughts were problematic, she became concerned, as many mentally ill new mothers might, that disclosing the true nature of her thoughts would result in her being designated an unfit mother.

It was after the birth of her second daughter that mania openly reared its head, resulting in a diagnosis of bipolar disorder with the specifier of “postpartum onset”.  Dyane described the surreal experience of hypergraphia, an uncommon symptoms involving excessive writing, including the juggling act of franticly writing while at the same time tandem breastfeeding her infant and toddler.

Dyane was hospitalized multiple times for her illness, and she recounted the sorts of challenges that are all too commonly faced by those with mental illness.  On one occasion she was handcuffed by police and taken to hospital in the back of a police car.  She was reported to Child Protective Services by one hospital psychiatrist, and when she reacted angrily she was placed in a seclusion room.  Being on locked wards that prevented from going outside and kept her cut off from internet and cell phone use had a detrimental effect on her recovery, and her hospitalizations worsened her anxiety and raised concerns about post-traumatic stress.  Mental health services could certainly benefit from incorporating this type of feedback.

Birth of a New Brain captures the frustration and desperation of treatment-resistant mental illness.  Dyane was trialled on numerous medications that triggered horrible side effects rather than a therapeutic benefit.  One particularly harrowing experience was with the antidepressant amitriptyline; taking a single dose led to intense suicidal thoughts requiring hospitalization.  Electroconvulsive therapy (ECT) was helpful, but she struggled with the considerable logistical and financial barriers that often go along with outpatient ECT.  For therapies like ECT to be at their most effective, it is important that mental health services work to minimize these sorts of barriers.

Over the years Dyane went off medications multiple times.  Despite giving it careful thought, consulting books by credible sources, and incorporating alternative strategies, her illness relapsed.  Finally she found success with an MAOI antidepressant, an option that has strong evidence of efficacy but is seldom considered due to the need for dietary restrictions. Once she was finally stabilized on an effective medication combination, she accepted that for her the reality was that medication would be an essential part of her wellness.  The book also describes a host of holistic strategies that Dyane incorporates as key elements of her treatment plan.

Birth of a New Brain offers hope to those struggling with mood disorders, and raises awareness about the little-known postpartum onset specifier for bipolar disorder.  By the end of the book the reader is left feeling as though Dyane is a dear friend who has bravely shared all and held nothing back.  While mental illness plays a starring role in the story, as Dyane concludes her final chapter, “I’m so much more than bipolar.  And so are you.”  Her book reminds us that no matter how hard the illness journey may be, recovery is possible.

Birth of a New Brain – Healing from Postpartum Bipolar Disorder

Foreword by the perinatal psychiatrist and acclaimed author Dr. Carol Henshaw. Available on Amazon in paperback & Kindle versions!

You can also find Dyane Harwood on her blog, Birth of a New Brain, and on Twitter @DyaneHarwood.

Psych meds 101: Anti-anxiety meds

anxiety written in Scrabble tiles

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.

Benzodiazepines

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.

Tolerance

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.

Withdrawal

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

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.

Buspirone

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.

Gabapentin, pregabalin

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

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

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

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……

 

Photo credit: Wokandapix on Pixabay

Pill Popper RN

horde of flying tablets and capsules

The title is a kind of weak ripoff from the Seinfeld-ian Pimple Popper MD, but still, it’s fairly apt.  I have major depressive disorder, and I take a boatload of pills.  Because my memory isn’t that great and I don’t want to forget to take them, I have them all laid out on a shelf in my bookcase.  If anyone comes into my living room chances are they’ll notice the mini pharmacy I’ve got going on, but I am so beyond caring about what people think about that.

In this post I’m going to break down the various things I’m putting into my body to try and stay afloat with my depression.  Medications will never be all of the picture, but for me they are an important part of my treatment plan.

Mirtazapine 30mg and venlafaxine 300mg: These are my two antidepressants.  I have always responded better to antidepressants with more activity related to norepinephrine than serotonin, so these two fit the bill.  The combo is sometimes referred to as “California rocket fuel” because of its potency.  Mirtazapine is actually most sedating at lower doses, so I’ve settled on the middle of the road 30mg dose because I didn’t sleep as well on higher doses.

Lithium 1200mg: I don’t have bipolar disorder, but lithium has actually been recognized for a long time as an effective augmentation strategy in major depressive disorder.  If I start feeling worse one of the first things my doctor and I consider is increasing my lithium, since I tend to respond fairly quickly to dose increases.  When my serum levels get higher, though, I tend to have increased problems with tremor and coordination, turning me into a complete klutz, complete with wipeouts on the sidewalk and falling down stairs.

Quetiapine 600mg: Atypical antipsychotics are also effective for treatment augmentation in depression.  Of the ones I have tried, quetiapine has been most effective for me.  It helps with my mood and is very reliable for getting to sleep.

Dextroamphetamine 15mg: I first tried dextroamphetamine a year and a half ago when I was really slowed down in both movement and thinking.  It helped, but I wasn’t keen on taking “speed” any longer than needed, so I only took it for about a month.  I restarted it earlier this year when I got really slowed down again.  It helped, but when I tried to decrease the dose my mood dropped.  Research has shown that it tends to be effective as an antidepressant augmentation strategy for only a couple of months or so, and then the effect tends to wear off; however, I’ve tried several times to decrease the dose and it makes me feel worse.  My doctor has a good attitude about it, and has no problem with me taking it on an ongoing basis when it’s clearly working.

Propranolol 10mg prn (as needed): Lithium gives me an intention tremor, which occurs with intentional movement as opposed to a resting tremor.  It’s worse if my lithium level is higher or if I’m worn out, and probably the dextroamphetamine doesn’t help either.  Propranolol helps keep it in check, and I tend to use it mostly for days that I’m working, since patients generally aren’t reassured about getting an injection if the nurse drawing it up has shaky hands.

nurse administering intramuscular injection

Lorazepam 0.5-1mg prn: Anxiety is generally not a prominent feature of my illness, so I’ve never needed to use lorazepam (Ativan) on a regular basis.  I find for me it’s most effective to get a bit of a numbing effect when I’m going into particularly stressful situations.  Since I use it so seldom, I’m able to get away with a small dose.

Min-Ovral: I have spent much of my adult life on birth control, but decided a couple of years ago to take a break.  When I got depressed last year, my hormones went crazy.  I was getting my period every 3 weeks and PMS was having a big impact on my mood.  Now I’m back on birth control and my hormones are steady and happy.  The estrogen in the Min-Ovral may also give my neurotransmitters a bit of a boost.

Omega-3 fatty acid plus vitamin D supplement: There have been research studies that have shown that omega-3’s have some beneficial effect on depression.  Vitamin D may also play a role in depression, and since I live on the Wet Coast of Canada where it rains for a good chunk of the year supplementation seems like a good way to go.

Multivitamin/mineral/antioxidant supplement: Besides helping my overall health, the goal with this is to have some effect on decreasing oxidative stress, which may play a role in depression.

L-methyfolate and vitamin B12 supplementation: I get these in an intramuscular injection every 2 weeks from my naturopath.  Both play a role in the methylation cycle that’s involved in neurotransmitter synthesis, and L-methylfolate in particular has been shown to be useful in depression.

So that’s me, Pill Popper RN.  What’s in your medicine cabinet?

 

Photo credits:

Qimono on Pixabay

huntlh on Pixabay

Psych meds 101: Mood stabilizers

pill_bottle

This is the 3rd in a series of primers on how psychiatric meds work.  The previous posts were on antidepressants and antipsychotics, and upcoming are anti-anxiety meds and sleep meds.  These are based on my professional knowledge as a mental health nurse and former pharmacist as well as my own experiencing taking these medications (although with a diagnosis of major depressive disorder I’ve never taken any of the anticonvulsant mood stabilizers).

Mood stabilizers work in a number of different ways to control signalling between nerve cells.  They are used to treat and prevent both mania and depression, although some drugs are more effective for one than the other.  They fall into 3 broad categories: lithium, anticonvulsants, and atypical antipsychotics.

Lithium

Lithium has been around for many years.  It works via a number of different mechanisms, including regulating genetic expression of various neuron-related factors, and boosting activity of the calming neurotransmitter GABA.  GABA counterbalances the excitatory neurotransmitter glutamate.  Lithium is effective for both mania and depression, and has been shown to decrease the risk of suicide.

Lithium is a type of salt, so blood levels are affected by kidney function and hydration status.  In the past, some people developed kidney damage from long-term lithium use, but that is rare now as we have a better understanding of what levels are safe.  People taking lithium need periodic bloodwork to check their lithium and creatinine levels (an indicator of kidney function).  Target levels are 0.6-1.2 mmol/L, with higher levels being needed in acute mania.  It takes 5 days after a dose change for blood levels to restabilize.

Lithium can potentially cause a lot of side effects: nausea/vomiting/diarrhea, tremor, weight gain,  hair loss, acne, frequent thirst, frequent urination, hypothyroidism, and effects on the heart.  And if that wasn’t enough, lithium toxicity (levels over 1.5) can cause confusion or even seizures and coma.  Yikes.  Except lithium works very well, and some people may have no side effects at all.

Lithium has definitely been effective for me.  I’m using it for depression, so I aim for levels between 0.65-0.8 depending on how I’m doing.  I have side effects, but for me the benefit outweighs the negatives.  I have a tremor, which is worse when I’m fatigued or if I’ve had to increase my dose.  Taking propranolol (a beta-blocker) helps with this.  I’ve gained weight on meds, but I’m on 2 other meds that cause weight gain so it’s hard to tell what’s causing what.

Anticonvulsants

These medications were initially developed as anti-seizure medications, but have since come to be used as mood stabilizers.  They affect signalling between nerve cells by acting at voltage-sensitive ion channels that allow sodium/calcium to flow in and out of neurons, and they also boost GABA neurotransmission.

Valproic acid/divalproex

These are essentially the same molecule, but divalproex can be formulated into an enteric-coated tablet that decreases stomach upset.  Valproic acid is effective for mania, but it is less clear how effective it is for bipolar depression.  Dosing is targeted to reach a blood level of 350-700 µmol/L.

Side effects include nausea, sedation, weight gain,  hair loss, tremor, negative effects on the liver, cessation of menstrual periods, and polycystic ovarian syndrome.  It is also teratogenic (causes harm to a developing fetus).  I talk more about this in my post on mental illness and childbearing.

Carbamazepine

Carbamazepine is most clearly effective for mania.  It affects the liver’s cytochrome P450 system, leading to interactions with a number of different medications.  It can also decrease the reliability of oral contraceptives.

Side effects include gastrointestinal upset, sedation, dizziness, impaired coordination, and negative effects on the liver, white blood cells, and platelets.

Lamotrigine

Lamotrigine is not effective for bipolar mania, and works best for the prevention of bipolar depression.  It interacts with both valproic acid and carbamazepine, requiring adjustments in dose.  It must be initiated slowly to decrease the risk of Stevens-Johnson syndrome, a type of severe rash.

Other side effects include dizziness, headache, double vision, drowsiness, impaired coordination, nausea, and weight gain.

Others

There are other anticonvulsants that have been tried in bipolar disorder but don’t necessarily have strong evidence to support their use.  These include levatiracetam and topiramate.  Gabapentin does not appear to be effective.

Atypical antipsychotics

The mechanism by which atypical antipsychotics have a mood stabilizing effect is not entirely clear, but may be related to their action at the 5HT2a serotonin receptor and resultant effects on glutamate, dopamine, norepinephrine, and serotonin signalling.  They are useful for both bipolar mania and depression.  Examples include lurasidone, aripiprazole, quetiapine, and olanzapine (which can be combined with the SSRI antidepressant fluoxetine for bipolar depression).

For more detail on atypical antipsychotics, please have a look at my post Psych Meds 101: Antipsychotics.

Role of antidepressants

There are two key problems with antidepressants in bipolar disorder: they don’t work particularly well, and there is a risk of triggering mania.  The International Society for Bipolar Disorder task force on antidepressant use found that evidence for antidepressant use is limited and weak, and as a result they could not broadly endorse the use of antidepressants in bipolar disorder.  An exception is fluoxetine, which is effective when used in tandem with olanzapine.

For more on antidepressants, you can read my post Psych Meds 101: Antidepressants

In conclusion…

I hope that this has all made sense and shone some new light on mood stabilizers.  If you have any questions please feel free to shoot them my way!

 

Photo credit: nosheep on Pixabay

Psych meds 101: Antipsychotics

neural_network

Welcome to the second post of my psych meds 101 series on how psychiatric medications work, this time focusing on antipsychotics.  In these posts I’m bringing together my knowledge as a mental health nurse, ex-pharmacist, and gal with depression who’s tried a boatload of meds, and hopefully putting out something that will make it easier to understand the nuts and bolts underlying the meds that so many of us take.  Knowledge is power, after all.

**note: I will exclusively use generic drug names, since brand names vary from country to country

**the other posts in this series are on antidepressantsmood stabilizers, and anti-anxiety meds.

Therapeutic uses

Needless to say the primary use of antipsychotic medications is in the treatment of psychosis.  There are a number of other uses, though, and the atypicals (I’ll get to that soon) are more versatile than the older drugs.  Atypical antipsychotics have an important role to play as mood stabilizers in bipolar disorder and to augment antidepressant regimens in major depressive disorder.  They may also be used for anxiety, and quetiapine is a common example of this.  Sedating antipsychotics such as quetiapine and methotrimeprazine may be used for sleep.  Haloperidol, a typical antipsychotic, is used in the treatment of delirium, a rapid-onset disturbance in cognition and orientation.

Mechanism of action

Antipsychotics work by blocking D2 dopamine receptors.  This impacts four major dopamine pathways in the brain, producing the therapeutic effect as well as side effects:

  • mesolimbic: dopamine overactivity in this pathway is associated with psychotic symptoms
  • mesocortical: this affects areas of the prefrontal cortex (the most evolutionarily advanced part of the brain) associated with cognition and mood
  • nigrostriatal: this pathway is associated with movement
  • tuberoinfundibular: this pathway regulates the hormone prolactin

There are two broad classes of antipsychotics: the “typicals” (older) and “atypicals“.  The key difference between these classes is that atypicals also block 5HT2a serotonin receptors.  This actually boosts dopamine signalling in the pathways other than the mesolimbic, which decreases the risk of side effects related to those 3 pathways.  Additionally, the effect on 5HT2a receptors contributes to a therapeutic effect on mood.  Another difference is that the atypicals are thought to move more rapidly on and off the D2 receptors, which is thought to allow for the full therapeutic effect without as much potential for side effects (this effect is referred to as “hit-and-run”).

To complicate matters, most antipsychotics aren’t very “clean”, in that they affect a number of other receptors aside from D2 and 5HT2a.  And that means side effects.

Side effects

While there is no way to predict which specific person is going to experience which particular side effects, in general medication side effect profiles are based on the types of receptors they interact with.

Movement-related symptoms

Extrapyramidal symptoms (EPS) occur most commonly with typical antipsychotics.  These are named for an area of the brain that is part of the nigrostriatal dopamine-signalling.  Excessively blocking dopamine in this region produces movement-related side effects, including tremor, rigidity, and akathisia (restlessness).  Anticholinergic medications such as benztropine can help to reverse these symptoms, due to an inverse relationship between the neurotransmitters acetylcholine and dopamine in this part of the brain.

Tardive dyskinesia (TD) is a slow onset, potentially reversible involuntary movement disorder that may affect the mouth, hands, and trunk.  It is caused by enduring changes in dopamine receptors in the basal ganglia as a result of long-term use of high-potency typical antipsychotics.  The risk of TD with atypicals is very low, and clozapine may actually improve TD symptoms.

Neuroleptic-induced deficit syndrome

This is a fancy name for causing apathy and related symptoms similar to negative symptoms of schizophrenia.  This can result from blocking dopamine receptors in the mesocortical pathway, and primarily occurs with typical antipsychotics.

Prolactin-related effects

Dopamine blockade in the tongue-twisting tuberoinfundibular pathway can increase levels of the hormone prolactin, which can result in some distressing side effects.  It can affect both sex drive and sexual function, and can also cause gynecomastia (development of breast tissue in men).  In general atypicals are less likely to cause this, although risperidone tends to carry a higher risk than other atypicals.

Metabolic effects

The atypicals win out over the typicals in many senses, but a major downside is that they do carry a risk for metabolic syndrome, including weight gain, increased cholesterol, and increased risk of diabetes.  This may be related to activity at histamine and 5HT2c serotonin receptors.  The big three are clozapine, olanzapine, and (to a lesser extent) quetiapine.  Aripiprazole and ziprasidone do not tend to be associated with weight gain.

Sedation

This can be related to effects on histamine, muscarinic, and alpha adrenergic receptors.  Individual medications vary in terms of which of these receptors they do or don’t effect, so there is a lot of variability in sedating effect.

Anticholinergic effects

The cholinergic signalling system is responsible for resting and digesting activities.  When antipsychotics disrupt this, the result can be things like dry mouth and constipation.  On a more positive note, this can decrease the likelihood of experiencing EPS.  Again, there is a lot of variation from medication to medication as to anticholinergic activity.

Drug-specific details

Quetiapine (atypical)

Quetipine affects serotonin and norepinephrine signalling in addition to its action on dopamine, and this likely contributes to its beneficial effects on mood.  The dose range varies widely, and for good antipsychotic effect the dose needs to be at the higher end of the range, approaching 1000mg/day.

Olanzapine (atypical)

Olanzapine is beneficial for mood.  It has a low risk of EPS.

Risperidone (atypical)

Of the atypicals, risperidone is the most likely to cause EPS and prolactin-related side effects.  Risperidone is metabolized by the body into paliperidone, which carries a somewhat lower risk of side effects.

Aripiprazole (atypical)

Aripiprazole has a unique mechanism of action.  It’s a partial agonist at D2 receptors, meaning it tries to create something along the lines of the Goldilocks just-right bowl of porridge.  It’s not sedating, and can actually help boost people’s energy.  It’s not associated with weight gain.  For all that it sounds like a pretty good drug, when I tried it several years ago I found my mood actually got worse.

Clozapine (atypical)

Clozapine can be a wonder drug for people whose psychotic symptoms are resistant to other medications.  It is the only antipsychotic that has been shown to decrease the risk of suicide in schizophrenia.  However, it can be problematic in terms of side effects.  It can increase the risk of seizures.  It can cause drooling, which can be quite bothersome for some people.  It can cause a dangerous drop in white blood cells, so bloodwork is required every 1-4 weeks.  When starting clozapine, there is a small risk of an inflammatory reaction in the heart called myocarditis.  It’s definitely not a first line medication, but sometimes you really do need to bring out the big guns.

Typical antipsychotics

Examples include loxapine, haloperidol, zuclopenthixol, and flupenthixol.  The latter three are often given as long-acting injections, although there are more alternatives now as a number of atypicals have become available for injection.

Long-acting injections

injectable medication

There are a a number of typical and antitypical medications available as long-acting (“depot”) injections.  These are generally given every 2-4 weeks.  They are given intramuscularly into the shoulder (deltoid), hip (ventrogluteal) or upper buttocks (dorsogluteal) sites.

There are a number of benefits to long-acting injections.  For some people it’s just easier to get an injection every few weeks than to take pills every day.  Long-acting injections produce very steady levels of medication in the blood, and it can be hard to replicate this even if someone is fairly consistent with taking oral medications.  Injections may be the treatment of choice for someone who is on some sort of community treatment order (the terminology and details around this vary depending on jurisdiction), particularly if they’re not keen on taking meds because they don’t have insight into their psychosis.

The downside to long-acting injections is that if people have side effects, they have to wait a while for the medication to clear out of their system.  This can be avoided by trialling someone on the oral version and then switching to the injectable.

In conclusion…

I hope that I haven’t confused you or totally turned you off of antipsychotics.  Personally I’ve taken quetiapine for years and will continue to take it for many more.  Antipsychotics can do a world of good, and I would say the most important thing is to work with your treatment provider to find what works best for you.

I’ll close with a brief anecdote.  I once had a client who had been extremely psychotic when I first started working with him.  We stabilized him on risperidone, and he responded beautifully except he was having sexual side effects.  We lowered his risperidone and added some olanzapine, and now several years later he is an amazing peer leader and advocate.  Meds gave this client his life back, and that’s priceless.

 

Image credit: Geralt on Pixabay

 

 

 

 

 

 

 

 

Psych meds 101: Antidepressants

pile of assorted medications

I can be a bit (okay more than just a bit) of a geek, and one of my big interests is how medications work.  Throw in the fact that I’m a mental health nurse, former pharmacist, and person who has tried piles of different psychiatric medication, and you get someone who will quite happily watch hours of continuing education webinars on the topic.

It can be really useful to understand how medications work, because it can make both the therapeutic effects and side effects make more sense.  This is the first of a series of psych meds 101 posts I’m going to write that will break down different classes of medications.  I’ll also address antipsychoticsmood stabilizers, anti-anxiety meds, and sleep meds.

Mechanism of Action

Most antidepressants affect the three major neurotransmitters implicated in depression: serotonin, norepinephrine, and dopamine.  Nerve cells (neurons) communicate with other neurons via connections known as synapses.  The neuron sending the signal is referred to as presynaptic, and the neuron receiving the signal is referred to as postsynaptic.  The presynaptic neuron releases neurotransmitter molecules in the synaptic cleft (the space between the two neurons), and the neurotransmitters act at specific receptors on the postsynaptic neuron.

diagram of synaptic cleftWhy does that matter?  Many antidepressants are reuptake inhibitors, meaning they block recycling pumps on the presynaptic side that would normally take up and recycle some of the neurotransmitter that had been released.  This means there is more neurotransmitter floating around the synaptic cleft, available to act at receptors on the postsynaptic neuron.  Over time, this actually changes the number of receptors that the postsynaptic neuron produces, which may explain the delayed onset of action for antidepressants.

Other antidepressants may block certain types of receptors on either pre- or post-synaptic neurons, and this may influence the release of one or more types of neurotransmitters.

Side Effects

A lot of medications are messy, in the sense that they don’t only do want them to.  Some antidepressants affect histamine receptors, and this can cause side effects such as sedation and weight gain.  Activity at muscarinic receptors can cause sedation, dry mouth, and constipation.

There are multiple different kinds of serotonin and norepinephrine receptors, and they impact various processes in the body.  When serotonin gets busy at certain types of receptors it can do things that we don’t want it to, causing things like insomnia, weight gain, or sexual dysfunction.  Norepinephrine can act at certain receptors to affect things like blood pressure, causing lightheadedness.

Classes of Antidepressants

Selective serotonin reuptake inhibitors (SSRIs):

These inhibit the activity of the presynaptic serotonin recycling pumps.  Escitalopram is the most “clean” in that it does what it’s supposed to and not much else.  Other medications in this class include citalopram, sertraline, fluoxetine, and paroxetine.

Serotonin and norepinephrine reuptake inhibitors (SNRIs):

These inhibit the presynaptic recycling pumps for both serotonin and norepinephrine.  Some people are not as responsive to meds that act on serotonin alone, and respond better when there is action on norepinephrine.  Drugs in this class include venlafaxine, desvenlafaxine, and duloxetine.

Norepinephrine and dopamine reuptake inhibitors (NDRIs):

Bupropion inhibits the presynaptic recycling pumps for norepinephrine and dopamine.  Because of the different mechanism of action, it can be used in combination with SSRI for a triple-whammy sort of effect.

Tricyclic antidepressants (TCAs):

These inhibit the recycling pumps for serotonin and norepinephrine.  However, they are quite “messy” and affect a number of different receptors, meaning they tend to cause more side effects.  They are dangerous in overdose because they can potentially disrupt the heart rhythm.  Several years ago a psychiatrist wanted to put me on nortriptyline, and while I reluctantly agreed, I soon stopped it because I didn’t think it was a safe medication to have at home given that I do get suicidal thoughts in the context of depression.  Other examples of TCAs include amitriptyline and imipramine.  This class of medications is also used to manage nerve pain.

Monoamine oxidase inhibitors (MAOIs):

These inhibit the monoamine oxidase (MAO) enzyme, which acts inside neuronal cells and is involved in breaking down serotonin, norepinephrine, and dopamine.  They are an older class of medications and despite being very effective antidepressants they are seldom used because of the need to restrict dietary intake of tyramine.  Tyramine is normally broken down in the gut by MAO, but if MAO is blocked by medication, tyramine is absorbed into the bloodstream and sends blood pressure through the roof.  This condition is referred to as hypertensive crisis.  Tyramine is found in a number of different foods, including aged cheeses and fermented foods.

Tranylcypromine is the most commonly used MAOI.  Moclobemide is a variation of an MAOI called a RIMA (reversible inhibitor of monoamine oxidase) that acts reversibly on the MAO enzyme, so that tyramine is still able to get broken down safely by MAO in the gut.

Other

There are a variety of other medications such as mirtazapine and vortioxetine that work in novel ways, which I won’t get into here.  The combination of mirtazapine and venlafaxine is sometimes referred to as “California rocket fuel”; this is part of my current treatment plan, and while I’m not getting a rocket fuel effect it has helped.  There are also other medications that can be used to augment antidepressant therapy, including lithium, atypical antipsychotic medications, and liothyronine (a form of thyroid hormone).

There are also new outside of the box treatments being studied such as ketamine, which affects the action of the neurotransmitter glutamate.  I am really excited about this, and will write more about it in future posts.

In conclusion…

If you’ve made it this far, good for you!  I hope you’ve found some of this useful, and maybe it’s even given you some added insight into medications you have taken or are taking.   In the upcoming post Psych Meds 101: Mood Stabilizers, I’ll talk about the treatment of bipolar depression, and why antidepressants have a limited role to play.

 

Photo by freestocks.org on Unsplash

How do you say antidepressant in Uzbek?

border control sign in English and Russian

I guess I should start by explaining what Uzbek is.  It’s the language of Uzbekistan, a former Soviet republic in central Asia that was part of the Silk Road that once wound through Asia.  It’s an area of the world where there are still people living the traditional nomadic lifestyle involving yurts, riding horseback, and drinking fermented mares’ milk (a delicacy I just couldn’t bring myself to try).

So how does this relate to antidepressants?  That’s where I have a story to tell.  In 2015, I spent 5 weeks backpacking in Uzbekistan, Kazakhstan, and Kyrgyzstan.  During that time, I was hauling around a veritable pharmacy: a sufficient supply of my 5 different psych meds, plus my standard round-up of just-in-case backpacking meds to cover motion sickness, travel’s diarrhea, and other such fun adventures.

I landed in Tashkent, the capital city of Uzbekistan, around 10pm.  I was exhausted from the long flight, and just wanted to fall into bed somewhere.  I thought it seemed a bit odd that the customs declaration form asked for a list of any medications I was carrying, but I dutifully listed them all.  The rather ghetto-seeming airport wasn’t inspiring much confidence, but I hoped that as is often the case my Canadian passport would get me waved right through.

When my turn in line came, I handed my declaration form to the customs officer.  He stared confusedly at my mammoth list of medications.  Then he wanted to see them, although I’m not sure why, as that didn’t seem to make things any easier.  He appeared to have no idea what to do, so he consulted some of his colleagues.  I told them that they were for depression, but they didn’t seem to have any idea what I was talking about.  There was much talking, looking confused, and phone calls until finally they waved me along.

I thought that would be the end of it; if only I could be so lucky.  I hadn’t booked a hostel room because it hadn’t struck me as necessary; I was an experienced traveller and had never had problems before.  Tashkent is no great tourist mecca, so that might have worked out okay, except there was some sort of international sporting competition going on in town and everything was booked up solid.

Central Asian yurt

By midnight, I had given up on Tashkent and instead turned up at the Uzbekistan-Kazakhstan border, thinking I might have better luck across the border.  Except that meant another customs declaration form, and much more confusion over my bag of meds.  The customs officers tried to be nice, but spoke very minimal English.  They wanted to know what the meds were for, and I didn’t think antidepressant would be in their lexicon, so I kept pointing at my head.  Maybe that made them more confused, or maybe it made me look more like a psych patient – who knows.  When they saw I’d just arrived in Uzbekistan that night, they decided they needed to call customs staff at the airport.  Talk about the blind leading the blinder.  Eventually I think they just took pity on me and let me go.

Travelling with psychiatric medications in non-Western countries can be a bit dicey, even aside from the issue of border crossings.  Replacement meds can be hard to come by if meds get stolen, and that’s something I always try to remain cognizant of.  That saved my butt on one occasion in India when I was sleeping in an upper bunk on an overnight train.  My backpack was shoved underneath the lower bunk, and during the night someone stole everything in the backpack other than clothing.  If my bag of meds hadn’t been tucked in beside me on the bunk, they would’ve been gone.

I haven’t really been well enough to travel in the last couple of years, but hopefully I’ll get back into it.  I still may be able to pull off my 40 by 40 goal: 40 countries visited by age 40.  And next time I go somewhere off the English-language track, I might look up the local word for antidepressant ahead of time… just in case.

 

Photo credits:

3dman_eu on Pixabay

Oziel Gómez on Unsplash