Judging a book by its cover

antique book

We live in a world that judges us on how we look.  Our body shape, our clothing, and any sign that we somehow deviate from what is “normal”, expected, or otherwise considered acceptable.  Mental illness is not always overtly obvious, but sometimes the effects of it are.  Hygiene may go out the window, and we emerge from our homes in dirty sweats and greasy hair.  Illness may slow us down or speed us up.  Eating disorders and other mental illnesses can affect our body shape, as can psychiatric medication.

I have a lithium-induced tremor, and I’ve been surprised by how often people comment on it. My tremor is worse with intentional movement than at rest, and this gets noticed often when I am paying for things in shops.  Clerks may come out with a condescending “take your time” or a concerned “are you ok?”  If I’m at a coffeeshop and carrying a wobbly mug to my seat, this will often elicit comments, either from staff or other customers.  I’m not sure why it’s anyone’s business, but it makes me feel very conspicuous.  I have a mostly invisible illness whose treatment has visible side effects.  I’m lucky that the antipsychotic that’s worked best for me (quetiapine) has a low potential to cause movement-related side effects like tardive akathisia.

Yet it’s hard sometimes to remember that I’m lucky.  One of my nursing jobs involves administering injections and teaching clients how to self-inject medications.  My hands are very much on display.  My tremor is worse with intentional movement than it is at rest, and I worry that clients will think I’m either nervous or incompetent.  I don’t really like either of those options.  I usually take propranolol before doing this kind of work to put a damper on the tremor, but if I’m tired/stressed/caffeinated the propranolol doesn’t do a whole heck of a lot.  I’ve seldom had clients comment, and if they do I brush it off as too much coffee, but the rest of the world seems to feel quite free to comment.

Another way I’m lucky is that I’ve never experienced a disordered relationship with eating.  I haven’t always been happy with my body, but it hasn’t impacted my relationship with food.  I’ve written before about illness, meds, and weight, but what comes to mind now as I’m writing this is questions about pregnancy.  My meds have caused the weight to pack on disproportionately on my lower abdomen.  The proportions have shifted around over time, but there was one particular summer that I was asked multiple times about my non-existent pregnancy.  I’m of the opinion that you should never ask a woman about being pregnant unless it looks like she’ll probably give birth tomorrow.  When others commented on my “pregnancy”, I felt like I had totally lost control over my body.  I felt really offended, less because of the very real psych med baby I was carrying around and more because others felt they had the right to talk about my body.

When I recently made the decision to add Botox to my depression treatment plan, a friend mentioned that they had thought about getting it cosmetically.  For some reason that made me feel icky.  And it’s not (at least I don’t think) so much that I would judge someone for getting a cosmetic procedure; it’s more that I don’t even care enough to wear makeup, and the thought of doing something to my body for cosmetic reasons seems utterly bizarre.  Maybe the issue is that I worry others will judge me for getting Botox.

This post has been a bit all over the place, but I guess my point is that we are judged.  No matter what we say, what we do, or what we look like, others will judge us.  We can’t stop it, much as we might wish to, so all that’s left is managing our own reactions.  And sometimes that’s much easier said than done.

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Do antidepressants work? What a new meta-analysis says.

meds

A recent paper published in the Lancet looked at how effective antidepressants are, and this has been reported on in the media.  Since media outlets don’t necessarily have strong research literacy, let’s take a look at what the paper itself has to say.  My earlier post on research literacy explains some of the terms I’ll be using here.

Full reference details for the paper:

  • Cipriani, A., et. al. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. The Lancet. doi:10.1016/S0140-6736(17)32802-7

A systematic review involves collecting a body of relevant literature on a topic using academic databases and search terms that are clearly specified, and then narrowing that down by applying certain criteria to find studies that are academically rigorous and fit with the research parameters being considered.  Typically, different investigators go through this process independently and then come to a consensus on which studies to include in the review.  The results are then evaluated to get a picture of the current state of the evidence.  A meta-analysis goes a step further by pooling the data from the various studies and then performing statistical analysis.

Inclusion criteria for this paper were:

  • randomized, double-blinded, controlled trials (either placebo-controlled or head-to-head trials of different antidepressants)
  • study participants were adults 18+
  • diagnosis of major depressive disorder
  • no more than 20% of participants in a study had bipolar disorder, treatment resistant depression, psychotic depression, or serious concurrent medical condition (while this might sound like a bad thing, when pooling numbers for a meta-analysis you want to make sure you’re comparing apples to apples)
  • evaluation of quality of evidence and risk of bias met specified academic standards

The outcome measures were response rate and acceptability (as measured by number of discontinuations due to side effects).  While ideally patients should be treated to full remission of symptoms, response rate is often used in research studies.  Response rate is defined as a 50% reduction in score on a standardized depression rating scale such as the Hamilton Depression Rating Scale (HAM-D).  For this meta-analysis they chose to evaluate outcomes at the 8-week point, and for the included studies that didn’t take ratings at 8 weeks this was imputed using statistical methods.

Findings:

  • All 21 antidepressants considered were more effective than placebo in adults with major depressive disorder.
  • In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants.
  • Fluoxetine, fluuvoxamine, reboxetine, and trazodone were the least efficacious drugs.
  • For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were the most tolerable.
  • The most discontinuations occurred with amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine.
  • Agomelatine was the only antidepressant with a lower dropout rate than placebo.

So, what does this paper not give information about, i.e. what conclusions are we not able to draw from it?

  • How effective these antidepressants are in terms of achieving full remission
  • Efficacy measures are only based on a 50% reduction in rating scale scores; there is no information about which particular clusters of symptoms are more or less likely to respond
  • What outcomes are beyond the 8-week point
  • Whether a specific antidepressant is or is not likely to be a) effective in a specific individual or b) more or less effective than any other antidepressant in that same individual
  • Whether a specific antidepressant is or is not likely to be tolerable for a specific individual
  • How often people experience side effects due to any of the antidepressants (it only looks at discontinuations due to side effects)
  • Whether any specific individual would or would not benefit from antidepressants at all
  • How well antidepressants work outside of the population considered in the review (i.e. under 18 years old or with treatment resistant depression, psychotic depression, or bipolar depression)

And what does all of this mean?  It’s important to keep in mind that a systematic review/meta-analysis such as this is only aiming to tell us very specific things.  The authors are deliberately comparing apples to apples so they can pool large groups of numbers and draw conclusions from that.  There’s a lot of real-world information that it doesn’t give us, but it’s worth keeping in mind that it makes no claims that it is.  The authors do not suggest that their findings can be extrapolated to answer any of the questions I’ve mentioned that the paper doesn’t give us information about.  What it does tell us is that antidepressants belong in our arsenal of available treatment strategies.  Anything more specific than that always needs to be a collaborative decision between the individual and their treatment team.

 

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Meds that can make you crazy (literally)

bottle labelled poison

We work so hard on our mental health, but sometimes we can get knocked down by an unexpected source: prescription medication.  Sure, we all know that some street drugs can adversely affect mental health, but there are also a number of prescription medications for conditions totally unrelated to mental health that can trigger symptoms of depression, mania, and psychosis.  The actual degree of risk varies depending on the specific medication and the patient context, and it’s always a question of risk versus benefit when deciding whether or not to take something.

Antibiotics: There have been a small number of reports of depression associated with norfloxacin and sulfa antibiotics.

Antiparasitics: Chloroquine and mefloquine, which are used in the prevention and treatment of malaria, can cause psychosis and mania.  My opinion is that there’s no reason for a person with a psych history to take either of these drugs, as there are other safe and effective alternatives.  If I’m visiting a malaria risk area, I always take Malarone, which is pricey but I can live with that to avoid psychosis; my second choice would be doxycycline.

Antivirals:  High-dose acyclovir, which can be used in the management or herpes or shingles, can trigger psychosis or depression.  Amantadine, which is used both as an antiviral to manage influenza and as an anti-Parkinsonian agent, can cause psychosis or mania, most frequently in the elderly.  Interferon is not technically an antiviral, but it is used in the treatment of viral hepatitis C; it can cause psychosis, mania, depression, and suicidal thoughts.  Luckily there are other treatment options available now, which is certainly more desirable for people living with mental illness.

Blood pressure and heart medications: Beta blockers have been linked with depression and mania.  Digoxin can trigger psychosis and depression.  The calcium channel blockers diltiazem and nifedipine have been associated with depression.  Diuretics in the same class as hydrochlorothiazide have been linked to depression and suicidal ideation.

Gastrointestinal: High doses of medications from the H2 receptor blocker class for acid reflux, such as ranitidine and cimetidine, can trigger psychosis, depression, and mania, particularly in the elderly or those with renal dysfunction.  Metoclopramide, which is used to boost GI motility, has been linked to mania and depression.

Analgesics and muscle relaxants: Abrupt discontinuation of the muscle relaxant baclofen can bring on depression, psychosis, or mania.  Cyclobenzaprine can also trigger mania and psychosis.  Some NSAIDs have been linked with psychosis and depression.

Hormonal agents:  Oral contraceptives can trigger depression; one study found that this happened in up to 15% of users.  The initial doses of thyroid hormones like levothyroxine in vulnerable patients can trigger mania, depression, and psychosis.  Steroids, including anabolic steroids and corticosteroids such as prednisone, can cause mania, depression, or psychosis, particularly when used at high dose or in withdrawal.  Topical or inhaled steroids have much lower systemic absorption and thus carry far less risk.

This is by no means an exhaustive list, and it’s not intended as a “do not take” list.  For most of these medications, the incidence of psychiatric side effects is low, and most people can take them without any problems.  I take the beta blocker propranolol on a fairly regular basis to manage my lithium-related tremor, and I’ve never noticed it impacting my mood.  I also take birth control and in my case it boosts my mood rather than making me depressed.  I’d say the important thing is to be aware that meds for physical health problems can impact your mental health, and listen to what your mind and body are telling you.

As a final word of caution, I would say be careful with steroids that are taken orally; in my experience they’re the top culprit for medication-related psychiatric symptoms.  Generally with something like prednisone it’s the kind of thing that if you need it, you need it, but there should always be a discussion with your doctor on how to do it most safely and make sure you’re monitored appropriately.

As always, knowledge is power!

 

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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……

 

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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!

 

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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

Let’s talk about sex (and mental illness)

couple kissing

What do mental illness and sex have to do with each other?  Quite a bit, actually, both in terms of the illness itself and the medications to treat it.

Let’s start with meds.  Antidepressants that affect serotonin (such as the SSRI class) can do a real number on sex drive/function.  This tends to be mediated by a particular type of serotonin receptor known as 5HT2a, which means that some antidepressants that affect serotonin are less likely to cause this problem, such as mirtazapine and vilazodone.  Another option is something like bupropion, which doesn’t act on serotonin receptors.  I talk more about antidepressants in my psych meds 101 post.

Antipsychotics can also be problematic (more on this in psych meds 101).  Antipsychotics work by blocking dopamine receptors, but if there is too much dopamine blockade along a certain pathway in the brain (the tuberoinfundibular pathway to  get really geeky with it), you disrupt levels of the hormone prolactin, and boom, you get sexual dysfunction.  Different antipsychotics vary in their potential to affect prolactin, so having sexual side effects with one doesn’t mean you will necessarily have the same effect with another medication.

Some mood stabilizers such as valproic acid are quite teratogenic, meaning they’re likely to cause fetal malformations.  This means reliable birth control is something that has to be considered along with everything else that goes with a mood disorder.  This is easier said than done for a woman in the midst of a manic episode.

woman lying in bed

Then there is the illness itself.  As a nurse, I’ve spoken to clients who are deeply ashamed of reckless sexual behaviour they’ve engaged in while manic or psychotic, things that under normal circumstances they would never even consider doing.  At the other end of the spectrum, depression can shut down sex drive and sexual function.  These are issues that it’s not easy or comfortable to talk about, so they tend to hide in the shadows, but they can have a huge effect both on an individual level and on a relationship.  I don’t have any great insights or answers to share with you, but I do think it’s important to talk about it.  It’s also worth considering sex as a potential barometer of your mental health.  I remember at one point when my depression was starting to improve I met a man who actually made me feel turned on, and I thought wow, this is the most normal thing that I’ve felt in a very long time.

I’ll close with a quick word on autoerotic activity, to borrow a term from Seinfeld.  Orgasm releases happy hormones like oxytocin and dopamine, so it seems to me a little bit of self-love once in a while can’t hurt.  And really, we all deserve some self-love, whether it’s in an erotic sense or not.

 

Image credits:

efes on Pixabay

Berzin on Pixabay

 

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