psychiatryQbank.com

What is the link between glaucoma and depression?

There is a circular link. Patients with glaucoma have higher risk of becoming depressed, and being exposed to antidepressants; some antidepressants can precipitate acute angle closure glaucoma (1). 

Why is this important for a psychiatrist?

It is easy to miss a history of glaucoma in a psychiatric assessment. Acute angle closure glaucoma, when occurs, is an ophthalmic emergency that can result in blindness if left unattended. Acute onset of ocular pain, headache, blurred vision, nausea and vomiting should prompt immediate attention.

Who is at risk?

The most common type of glaucoma is open-angle type. This usually does not result in an ophthalmic emergency. So psychotropics  have no effect on open-angle glaucoma. Psychotropics can precipitate narrow angle glaucoma especially in female patients, those of advanced age, patients with a family history of narrow angle glaucoma, being far-sighted and being of Asian, Hispanic or Inuit ethnicity.

What antidepressant drugs can worsen angle closure glaucoma?

Medications with anticholinergic properties or adrenergic agonist effects can precipitate acute angle closure. Serotonergic agents are also increasingly reported to be associated with glaucoma.

What antidepressant drugs should I avoid in a patient known to have glaucoma?

• Beware of clomipramine, imipramine, amitryptyline 
• Caution is needed with SSRIs such as citalopram, escitalopram, fluoxetine and paroxetine as well as the SNRI venlafaxine. SSRI treatment >365 days and the use of higher doses of SSRIs (≥1 defined daily dose) are associated with greater risk of glaucoma incidence (3).
• Caution is warranted for using MAO inhibitors such as tranylcypromine or phenelzine as well.
• Interestingly, bupropion reduces intraocular pressure in open angle glaucoma, but like SSRIs, worsens narrow-angle glaucoma.

Can I use antipsychotics in a patient with glaucoma?

Certain antipsychotics, though weaker anticholinergics than tricyclics, can induce glaucoma. These include trifluoperazine, perphenazine, fluphenazine, zuclopenthixol as well as olanzapine and quetiapine.

What other drugs in my practice should I be wary of?

Benzodiazepines (diazepam and alprazolam) can induce relaxation of the sphincter muscle of the iris and precipitate angle closure in patients who are at risk. Topiramate is also associated with angle closure risk. Not to forget that some patients may also be using ecstasy, marijuana or cocaine, all of which may also precipitate angle closure.

Is there any antidepressant that I can safely use in angle-closure glaucoma?

While no single drug can be confidently recommended (all of them urge caution for glaucoma in their monographs), it is prudent to:

1. Elicit history and clarify the type of glaucoma
2. Request ophthalmic evaluation before treatment onset 
3. Start medications with least anticholinergic propensity and avoid polypharmacy
4. Educate the patient on symptoms of acute worsening (pain, headache, halos and blurred eye-sight, red eye,  excess lacrimation)
5. Arrange for regular intraocular pressure monitoring while taking treatment

Where can I read more?

1. Chen YY, et al. The association between glaucoma and risk of depression: a nationwide population-based cohort study. BMC ophthalmology. 2018 Dec 1;18(1):146. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013853/
2. Yang MC, Lin KY. Drug-induced Acute Angle-closure Glaucoma: A Review. Journal of Current Glaucoma Practice. 2019 Sep;13(3):104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221246/
3. Chen VC, et al. Effects of selective serotonin reuptake inhibitors on glaucoma: A nationwide population-based study. PLOS one. 2017 Mar 3;12(3):e0173005. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5336262/
4. Symes RJ, Etminan M, Mikelberg FS. Risk of angle-closure glaucoma with bupropion and topiramate. JAMA ophthalmology. 2015 Oct 1;133(10):1187-9. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2381574

Stimulants have been intuitively considered as treatment options for depression for a very long time.  It is often said that Freud treated his own depression by snorting cocaine. 

Methylphenidate (Ritalin) was first systematically studied in the treatment of depression in the UK in 1958 by Robin & Wiseberg, with spectacularly negative results. But the allure of the rapid action and the broad monoaminergic effects of stimulants meant that we clinicians never lost our interest in this class of drugs for treating depression! In many cases of treatment resistance as well as in psycho-oncology practice, stimulants are used for depressive symptoms.

To date, there have been 2 RCTs on methylphenidate, 2 on modafinil, 3 on lisdexamfetamine (Vyvanse) as augmentation agents to antidepressants (predominantly SSRIs or venlafaxine) but none of them have demonstrated a convincing clinical or statistical advantage for efficacy (1).

Nevertheless, for specific forms of depression, such as bipolar depression, there is some support for psychostimulant augmentation ( 1 RCT on modafinil; 4 RCTs on armodafinil). I say ‘some’ support, as 16 patients with bipolar depression need to be augmented with modafinil for one additional subject to achieve remission. But it is worth noting that you are 4 times more likely to help than harm a patient with bipolar depression when trying this adjunct treatment (The likelihood to be helped or harmed (LHH = NNH/NNT = 4.26) (2).

Various speculations exist to explain the spectacular lack of supportive evidence for psychostimulants in depression.

1.  Stimulants may only benefit a subgroup of depressed patients with excess sleepiness and lack of drive (i.e., atypical depression) (3).
2. For a given patient, some [i.e. neurocognitive (executive dysfunction) and neurovegetative (melancholic)] but not all features of depression may respond better (4).

So what do we need to know when considering the use of stimulants for depression in practice?

1. Evidence to use stimulants as monotherapy or adjuvants for MDD is weak, not supportive of routine consideration. Ritalin, Vyvanse and Modafinil have been studied in this regard.
2. For bipolar depression, modafinil has more encouraging evidence base (armodafinil at 150mg/day or modafinil at 200mg/day) as adjuvant to various combinations of mood stabilisers
3. If you are planning to use stimulants in MDD or bipolar depression, please remember that (1) combining stimulants with TCAs or MAOIs can increase the risk of hypertensive crisis as well as serotonin syndrome (2) most controlled trials have been short-term studies (~8 weeks), so there is not much leg to stand on when using stimulants for long periods when a response is not forthcoming.
4. It is important to keep in mind the habit forming potential of stimulants. “If there is one person who can be held responsible for the emergence of cocaine as a recreational pharmaceutical, it was Freud.” – Dominic Streatfeild, in the book “Cocaine: An Unauthorized Biography”

References

1. Faraone SV. The pharmacology of amphetamine and methylphenidate: relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. Neuroscience & Biobehavioral Reviews. 2018 Apr 1;87:255-70.
2. Nunez NA, Singh B, Romo‐Nava F, Joseph B, Veldic M, Cuellar‐Barboza A, Cabello Arreola A, Vande Voort JL, Croarkin P, Moore KM, Biernacka J. Efficacy and tolerability of adjunctive modafinil/armodafinil in bipolar depression: A meta‐analysis of randomized controlled trials. Bipolar disorders. 2020 Mar;22(2):109-20.
3. Hegerl U, Hensch T. Why do stimulants not work in typical depression?. Australian & New Zealand Journal of Psychiatry. 2017 Jan;51(1):20-2.
4. McIntyre RS, Lee Y, Zhou AJ, Rosenblat JD, Peters EM, Lam RW, Kennedy SH, Rong C, Jerrell JM. The efficacy of psychostimulants in major depressive episodes: a systematic review and meta-analysis. Journal of Clinical Psychopharmacology. 2017 Aug 1;37(4):412-8.

Do you know of a condition “which causes such suffering that it should be known by every physician”?(1) That is what Ekbom, the neurologist who described this condition, said in 1960.

This condition, used to be known as  anxietas tibiarum (the anxiety of the shin bone), is now called RLS or Restless Leg Syndrome.

RLS is seen in several medical conditions such as iron deficiency, chronic kidney disease and peripheral neuropathy, all of which are also associated with higher frequency of depression. Antidepressant use can also precede new-onset or worsening of RLS in some cases, though a clear-cut causal association is still controversial (2).

Different antidepressants have varying strength of association with RLS.

This figure, based on 2 reviews (3, 4), provides a quick summary.

Have you ever come across antidepressant related RLS? How did you manage it? Add your comments below!

References:

(1) Winkelman, J. Restless Legs Syndrome. History of Neurology: Seminal Citations. Arch Neurol. 1999;56(12):1526-1527.

(2) Dunvald AC, Henriksen DP, Hallas J, Christensen MM, Lund LC. Selective serotonin reuptake inhibitors and the risk of restless legs syndrome: a symmetry analysis. European Journal of Clinical Pharmacology. 2020 Feb 16:1-4.

(3) Kolla BP, Mansukhani MP, Bostwick JM. The influence of antidepressants on restless legs syndrome and periodic limb movements: A systematic review. Sleep Med Rev. 2018;38:131-140

(4) Rottach KG, Schaner BM, Kirch MH, et al. Restless legs syndrome as side effect of second generation antidepressants. J Psychiatr Res. 2008;43(1):70-75.

Often we request urine drug screening when we suspect possible drug use, but cannot trust what the patient says. What if this test declares a non-user as being positive? Who will you believe in – the test or the tested? 

One of my patients who was on treatment for depression for more than 3 years, landed in a new job after much struggle. I was genuinely pleased for him. He was undergoing routine paperwork before taking up the job in the next few days. Then, out of the blue, he rang my office in despair.

His new employers asked for a random urine drug test, and he turned positive for amphetamine and LSD (Lysergic Acid Diethylamide). Yikes!

 I knew him quite well. He was not a user. He was devastated.

We set out to find the reasons for this false-positivity. Could it be contamination? Or a genuine lab mix-up?

It turned out that the antidepressant that he was on, desipramine, can cause notorious false positive results for both amphetamine and LSD. Holy Moly!

We know how important urine drug screen testings are for our clinical practice, but these are also used in educational, employment and legal settings. Hence, it is very important for clinicians to interpret these test results and have knowledge of false positive results. The misinterpretation of results can have negative consequences for the individuals being tested. 

Learn more about potential false positive drug screen when attending our course.

Reference:

• Saitman A, Park HD, Fitzgerald RL. False-positive interferences of common urine drug screen immunoassays: a review. J Anal Toxicol. 2014;38(7):387-396. doi:10.1093/jat/bku075

Journalists write a lot. I mean, a lot. They cannot afford to wait for the ‘writing’ mood. But how can you write meaningfully when your “brain is on fire”? A 24 year old New York Post reporter, Susannah Cahalan, had her “brain on fire” for nearly a month.  

In her own words¹, she says, “I started [acting] very psychotic. I believed that I could age people with my mind. If I looked at them, wrinkles would form, and if I looked away, they would suddenly, magically get younger. And I believed that my father had murdered my stepmother. I believed all these incredibly paranoid — a huge, extreme example of persecution complex. And then as the days went on, I stopped being as psychotic, and I started entering into a catatonic stage, which was characterized by just complete lack of emotion, inability to relate, or to read, or hardly to be able to speak”

That description, her age as well as the combination of symptoms should tell us she is experiencing a typical psychotic episode. Right?

No! Susannah Cahalan’s psychotic break was anything but typical. 

And it was not antipsychotics that got her out of this “month of madness”, as she puts it.

It turned out she had anti-NMDA encephalitis. While rare, it is important to know the ‘red flags’ for this condition, as it can be easily missed for schizophrenia or a mood disorder, but near-totally reversed with the right type of immunotherapy. 

There are also many other conditions that can set your brain on psychotic fire, though pouring antipsychotics may not quench all the flames. There is more on the topic of Atypical Psychosis in our Qbank materials.

Have you ever come across anti-NMDA encephalitis? How long did it take before your patient was rightly diagnosed? Add your comments below!

Reference: 

1. https://www.npr.org/2012/11/14/165115921/a-young-reporter-chronicles-her-brain-on-fire

Clozapine as a treatment option has many strengths. But it also has some weaknesses. This week I had a patient who has been stable on clozapine for ages, but now has a new problem related to this drug.

My patient has a well known problem associated with clozapine that is fortunately rare – obsessional phenomena. 

Till date, we do not know what makes some patients on clozapine to develop obsessions and compulsions. Glutamate modulation, serotonergic 5-HT2C hypersensitivity and dopaminergic ‘escape’ after chronic blockade are all suspected but none of these mechanisms are proven to be causal¹.  

So how can we manage this?

1. Clozapine dose reduction is a popular strategy in practice, though this may not be always practical when the patient is still unwell with psychotic symptoms.
2. Adding a serotonin reuptake inhibitor such as fluoxetine or sertraline may help, as long as clozapine/nor-clozapine levels are monitored.
3. Adding aripiprazole, a 5-HT1A partial agonist, seems to be helpful in some studies. 
4. Other options include the popular anti-OCD treatment clomipramine as well as glutamatergic modulators such as lamotrigine.

Have you come across clozapine induced obsessions in your practice? What worked for you? 

Add your comments below! 

1. Kim DD, Barr AM, White RF, Honer WG, Procyshyn RM. Clozapine-induced obsessive–compulsive symptoms: mechanisms and treatment. Journal of psychiatry & neuroscience: JPN. 2019 Jan;44(1):71.

In psychiatry, we have been trying to reach the brain via various parenteral routes for a long time. Some historians claim that Neolithic ‘trephination’ observed in the Stone Age skulls may in fact be an attempt to treat psychiatric conditions ¹. We have been spectacularly successful with some non-pharmacological parenteral therapies. Brain stimulation techniques are commonly employed ‘parenteral’ approaches forming a substantial portion of our prescribed treatments now. 

The last decade has seen a less invasive pharmacological approach for parenteral therapy. Intranasal delivery of drugs seem to reach the central nervous system by directly crossing the blood-brain barrier via olfactory bulb pathways. For drugs that do cross this barrier effectively, intranasal delivery offers a means to circumvent the side effects of systemic administration.

What drugs look promising in this regard?

The 3 most promising agents at present are

1. Intranasal ketamine for depression
2. Intranasal oxytocin for various conditions where reduced empathy is prominent
3. Intranasal insulin for various neurodegenerative and cognitive syndromes²

Of these 3, the one that is ready for clinical use is the s-enantiomer of ketamine. You can find more information about the evidence for intranasal esketamine use in our Qbank materials.

• 1. Faria MA. Neolithic trepanation decoded- A unifying hypothesis: Has the mystery as to why primitive surgeons performed cranial surgery been solved? Surg Neurol Int 2015;6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427816/

• 2. Reger MA, Watson GS, Green PS, et al. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 2008;70:440–8.

This is not an uncommon problem. In some cases the psychiatric symptoms may indeed be precluding success in securing jobs (e.g. ADHD), working capacity (depression) or contributing to debts (mania). But in most cases, treating the psychiatric symptoms along is unlikely to eliminate the financial hardships.

It is important to know what local resources are available for social assistance, including the services of a Social Worker.

At PsychiatryQbank, we believe there are several “Social Interventions” that a physician can do.

We asked Dr. Priya Sabesan, a psychiatrist who works at a busy Urgent Consultation setting, to share some of her views on social interventions in office-based practice.

She says there are many things that we can do, that are likely to be directly helpful to our patients.

The 3 ‘high-yield’ social intervention measures, in her practice are:

1. Focusing on 4 key domains of social disability – housing, work, education & finances
2. Writing support letters to relevant organizations
3. Providing strong and effective written information to support disability applications

She has put together 3 easy reference slides that cover practice points for these measures. You can find them in the flipbook link HERE.

What other social interventions do you think are relevant to your practice? Drop a comment below!

Twenty five years ago, there were 2 groups of children. Some were poor, others were not. 

They all lived in a rural region, and their families agreed for regular annual research interviews for 8 years to track symptoms of mental illnesses. 

All was well for 4 years, and then an interesting thing happened.  A portion of this rural community suddenly had a significant increase in their income, as a new casino opened in their neighbourhood, and the casino’s operators distributed their profits to every family, every 6 months. Many other businesses came to that region, supporting the casino, and eventually nearly half of the families living in that locality were not poor anymore.

Moving out of poverty had an immense effect on the children. The frequency of psychiatric symptoms considerably dropped over the next 4 years; by the fourth year the symptom level was the same in children who moved out of poverty as in children who were never poor. But adding to the income of those families who were never poor in the first place had no effect on the frequency of psychiatric symptoms.

Income intervention improved behavioural symptoms, but did not have much effect on the emotional symptoms.

This fascinating ‘quasi-experimental’ study is called The Great Smoky Mountains Study1. It was led by Elizabeth Jane Costello of Duke University, and published in 2003 in the JAMA. Cited more than 1200 times, it is a classical paper that argues strongly for us to do what we can to provide social interventions to our patients.  

What do you think about this study? Does this change your perception of social interventions in psychiatry?

More on this in our next blog post! 

1. Costello EJ, Compton SN, Keeler G, et al. Relationships Between Poverty and Psychopathology: A Natural Experiment. JAMA 2003;290:2023–9.