ERA Series 6: Neuropsychiatry
calendar
11 Jul, 16

Depression: Screening and Diagnosis

Significance
  • Higher prevalence of depression reported in HIV-positive persons (20-40% versus 7% in general population)
  • Significant disability and poorer treatment outcomes associated with depression

Screening and Diagnosis

Who?

How to screen?

How to diagnose?

Screening of all HIV-positive persons recommended in view of the high prevalence of depression

Populations at particular

high risk

  • Positive history of depression in family
  • Depressive episode in personal history
  • Older age
  • Adolescence
  • Persons with history of drug addiction, psychiatric, neurologic or severe somatic co-morbidity
  • Use of EFV
  • Use of neurotropic and recreational drugs
  • As part of investigation of neurocognitive impairment
  • Screen every 1-2 years
  • Two main questions:

1. Have you often felt depressed, sad or without hope in the last few months?

2. Have you lost interest in activities that you usually enjoy?

  • Specific symptoms in men

- Stressed, burn out, angry outbursts, coping through work or alcohol

  • Rule out organic cause (such as hypothyroidism, hypogonadism, Addison’s disease, non-HIV drugs, vitamin B12 deficiency)

Symptoms – evaluate

regularly

    A. At least 2 weeks of depressed mood

OR

B. Loss of interest

OR

     C. Diminished sense of pleasure

PLUS 4 out of 7 of the following:

1. Weight change of ≥5% in one month or a persistent change of appetite

2. Insomnia or hypersomnia on most days

3. Changes in speed of thought and movement

4. Fatigue

5. Feelings of guilt and worthlessness

6. Diminished concentration and decisiveness

7. Suicidal ideation or a suicide attempti

i. EFV has been associated with a higher risk of suicidal ideation

Depression: Management

Degree of depression

No. of symptoms

(A,B or + 4/7)

Treatment

Consultation with expert

No

<4

No

 

Mild

4

  • Problem-focused consultation
  •  Consider antidepressant treatmenti
  • Recommend physical activity
  • Always, if treating physician is unfamiliar with use of antidepressants
  • If depression is not responding to treatment
  • If person has suicidal ideation
  • In case of complex situations such as drug addiction, anxiety disorders, personality disorders, dementia, acute severe life events

Intermediate

5-6

Start antidepressant

Treatmenti

Severe

>6

Refer to expert (essential)

i. See Drug-drug Interactions between Antidepressants and ARVs
 
If a person is diagnosed with depression, switching off EFV to another third ARV drug according to switch rules is recommended.

Algorithm for Diagnosis and Management of HIV-associated Neurocognitive Impairment  (NCI) in Persons without Obvious Confounding Conditions

ERA-Book-6_1

Abbreviations: CSF cerebrospinal fluid; GDR genotypic drug resistance test; HAD HIV-associated dementia; MND mild neurocognitive disorder; MRI brain magnetic resonance imaging; NP neuropsychological

i. Obvious confounding conditions:
1. Severe psychiatric conditions
2. Abuse of psychotropic drugs
3. Alcohol abuse
4. Sequelae from previous CNS-OIs or other neurological diseases
5. Current CNS-OIs or other neurological diseases
 
ii. The following 3 questions may be used to guide physician assessment:
1. Do you experience frequent memory loss (e.g. do you forget the occurrence of special events even the more recent ones, appointments, etc.)?
2. Do you feel that you are slower when reasoning, planning activities, or solving problems?
3. Do you have difficulties paying attention (e.g. to a conversation, book or movie)?
For each question, answers could be as follows: a) never, b) hardly ever, or c) yes, definitely. HIV-positive persons are considered to have an “abnormal” result when answering “yes, definitely” on at least one question.
 
iii. See Depression: Screening and Diagnosis
 
iv. NP examination will have to include tests exploring the following cognitive domains: fluency, executive functions, speed of information processing, attention/working memory, verbal and visual learning, verbal and visual memory, motor skills plus assessment of daily functioning.
 
v. Neurological examination, brain MRI and CSF examination are required to exclude other pathologies and to further characterize HIV-associated NCI, by including assessment of CSF HIV-VL level and, where appropriate, evidence for genotypic drug resistance (GDR) in a paired CSF and plasma sample.
 
vi. NCl includes
1. marked acquired impairment in cognitive functioning involving at least 2 cognitive domains, as documented by performance of at least 1 SD below the mean for age-education appropriate norms on NP tests
2. interference in daily functioning
3. no evidence of another pre-existing cause for the dementia
 
vii. CSF escape definition either CSF VL >50 and plasma HIV-VL <50 copies/mL- or both CSF and plasma HIV-VL >50 copies/mL, with CSF HIV-VL >0.5 log10 higher than plasma HIV-VL
 
viii. Including all situations that do not fulfil the CSF escape definition
 
ix. Definition of ‘potentially CNS-active’ drugs:
 
ARV drugs with either
1. demonstrated clear CSF penetration when studied in healthy HIV-positive populations (concentration above the IC90 in > 90% examined persons)
2. proven short-term (3-6 months) effi cacy on cognitive function or CSF HIV-VL decay when evaluated as single agents or in controlled studies in peer-reviewed papers
  • Drugs with demonstrated clear CSF penetration:
  • NRTIs: ZDV, ABC*
  • NNRTIs: EFV**, NVP
  • PI/r, IDV/r, LPV/r, DRV/r*
  • INSTI: DTG
  • Other classes: MVC
  • Drugs with proven clinical efficacy:
  • NRTIs: ZDV, ABC
  • PI/r: LPV/r

* When administered twice daily. Once-daily administration of these drugs, although common in clinical practice, has not been studied extensively with regard to CNS effects/CSF penetration and may have different CNS activity.

** EFV should be used cautiously in HIV-positive persons with NCI because of its detrimental effects on neurocognitive function in a RCT and potentially confounding CNS effects.

Classification, Doses, Safety and Adverse Effects of Antidepressants

Mechanisms &

classification

Start

dose

Standard

dose

Lethality in

overdose

Insomnia

and

agitation

Sedati-on

Nausea or GI effects

Sexual

Dysfuncti-on

Weight gain

mg/day

Selective serotonin-reuptake inhibitors (SSRIs)i

Paroxetine

10-20

20-40

Low

+

-/+

+

++

++

Sertraline

25-50

50-150

Low

+

-/+

+

+

+

Citalopram

10-20

20-40

Low

+

-/+

+

+

+

Escitalopram

5-10

10-20

Low

+

-/+

+

+

+

Mixed or dual-action reuptake inhibitors

Venlafaxine

37.5-75

75-225

Moderate

++

-/+

+

+

-/+

Mixed-action newer agents

Mirtazapine

30

30-60

Low

-/+

++

-/+

-/+

++

None

Moderate

++ Severe

For many persons, SSRI induction may be associated with adverse effects (GI tract, dizziness, anxiety, panic attacks). Commencing at lower doses (i.e. 10, 25 & 10 mg for Paroxetine, Sertraline and Citalopram, respectively) and increasing to the above starting doses after 4 to 7 days, if tolerated, may reduce such effects.

Drug-drug Interactions between Antidepressants and ARVs

Antidepressants

ATV/r

DRV/c

DRV/r

LPV/r

EFV

ETV

NVP

RPV

MVC

DTG

EVG/c

RAL

SSRI

citalopram

a

a

escitalopram

a

a

fluvoxamine

E

fluoxetine

paroxetine

↑↓?

↑↓?

↓39%

↑↓?

↑↓?

sertraline

↓49%

↓39%

SNRI

duloxetine

↑↓

↑↓

↑↓

venlafaxine

D

TCA

amitriptyline

a

a

clomipramine

a

a

desipramine

a

↑5%a

doxepin

imipramine

a

a

nortriptyline

a

a

trimipramine

TeCA

Maprotiline

mianserine

mirtazapine

Others

bupropion

↓57%

↓55%

↑?

lamotrigine

↓32%

↓50%

nefazodone

↓E

↓E

↓E

E

E

St. John’s wort

D

D

D

D

D

D

D

D

D

Db

D

trazodone

↑ potential elevated exposure of the antidepressant

potential decreased exposure of the antidepressant

↔ no significant effect
D potential decreased exposure of ARV drug
E potential elevated exposure of ARV drug
A ECG monitoring is recommended
B The US Prescribing Information recommends that co-administration should be avoided as there are insufficient data to make dosing recommendations. Numbers refer to decreased AUC of the antidepressant as observed in drug-drug interaction studies.
SSRI selective serotonin reuptake inhibitors
SNRI serotonin and norepinephrine reuptake inhibitors
TCA tricyclic antidepressants
TeCA tetracyclic antidepressants

Reference

EACS Guidelines version 8.0 - October 2015